VCV000024973.44 - ClinVar

NM_001370658.1(BTD):c.73G>A (p.Gly25Arg)

Germline

Classification

The aggregate germline classification for this variant, typically for a monogenic or Mendelian disorder as in the ACMG/AMP guidelines, or for response to a drug. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the aggregate classification.

(12)

Stars represent the aggregate review status, or the level of review supporting the aggregate germline classification for this VCV record. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. The number of submissions which contribute to this review status is shown in parentheses.

Conflicting classifications of pathogenicity
Uncertain significance(3); Benign(3); Likely benign(4)

criteria provided, conflicting classifications

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

Identifiers

NM_001370658.1(BTD):c.73G>A (p.Gly25Arg)

Variation ID: 24973 Accession: VCV000024973.44

Type and length

single nucleotide variant, 1 bp

Location

Cytogenetic: 3p25.1 3: 15635512 (GRCh38) [ NCBI UCSC ] 3: 15677019 (GRCh37) [ NCBI UCSC ]

Timeline in ClinVar

	First in ClinVar Help The date this variant first appeared in ClinVar with each type of classification.	Last submission Help The date of the most recent submission for each type of classification for this variant.	Last evaluated Help The most recent date that a submitter evaluated this variant for each type of classification.
Germline	Nov 10, 2017	Oct 20, 2024	Aug 1, 2024

HGVS

Nucleotide	Protein	Molecular consequence
NM_001370658.1:c.73G>A MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_001357587.1:p.Gly25Arg	missense
NM_000060.4:c.133G>A	NP_000051.1:p.Gly45Arg	missense
NM_001281723.4:c.73G>A	NP_001268652.2:p.Gly25Arg	missense
NM_001281724.3:c.73G>A	NP_001268653.2:p.Gly25Arg	missense
NM_001281725.3:c.73G>A	NP_001268654.1:p.Gly25Arg	missense
NM_001281726.3:c.73G>A	NP_001268655.2:p.Gly25Arg	missense
NM_001323582.2:c.73G>A	NP_001310511.1:p.Gly25Arg	missense
NM_001370752.1:c.73G>A	NP_001357681.1:p.Gly25Arg	missense
NM_001370753.1:c.73G>A	NP_001357682.1:p.Gly25Arg	missense
NM_001407364.1:c.73G>A	NP_001394293.1:p.Gly25Arg	missense
NM_001407365.1:c.73G>A	NP_001394294.1:p.Gly25Arg	missense
NM_001407366.1:c.73G>A	NP_001394295.1:p.Gly25Arg	missense
NM_001407367.1:c.73G>A	NP_001394296.1:p.Gly25Arg	missense
NM_001407368.1:c.73G>A	NP_001394297.1:p.Gly25Arg	missense
NM_001407369.1:c.73G>A	NP_001394298.1:p.Gly25Arg	missense
NM_001407370.1:c.73G>A	NP_001394299.1:p.Gly25Arg	missense
NM_001407371.1:c.73G>A	NP_001394300.1:p.Gly25Arg	missense
NM_001407372.1:c.73G>A	NP_001394301.1:p.Gly25Arg	missense
NM_001407373.1:c.73G>A	NP_001394302.1:p.Gly25Arg	missense
NM_001407374.1:c.73G>A	NP_001394303.1:p.Gly25Arg	missense
NM_001407375.1:c.73G>A	NP_001394304.1:p.Gly25Arg	missense
NM_001407376.1:c.73G>A	NP_001394305.1:p.Gly25Arg	missense
NM_001407377.1:c.73G>A	NP_001394306.1:p.Gly25Arg	missense
NM_001407378.1:c.73G>A	NP_001394307.1:p.Gly25Arg	missense
NM_001407379.1:c.73G>A	NP_001394308.1:p.Gly25Arg	missense
NM_001407380.1:c.73G>A	NP_001394309.1:p.Gly25Arg	missense
NM_001407381.1:c.73G>A	NP_001394310.1:p.Gly25Arg	missense
NM_001407382.1:c.73G>A	NP_001394311.1:p.Gly25Arg	missense
NM_001407383.1:c.73G>A	NP_001394312.1:p.Gly25Arg	missense
NM_001407384.1:c.73G>A	NP_001394313.1:p.Gly25Arg	missense
NM_001407386.1:c.73G>A	NP_001394315.1:p.Gly25Arg	missense
NM_001407388.1:c.73G>A	NP_001394317.1:p.Gly25Arg	missense
NM_001407390.1:c.73G>A	NP_001394319.1:p.Gly25Arg	missense
NM_001407392.1:c.73G>A	NP_001394321.1:p.Gly25Arg	missense
NM_001407394.1:c.73G>A	NP_001394323.1:p.Gly25Arg	missense
NM_001407395.1:c.73G>A	NP_001394324.1:p.Gly25Arg	missense
NM_001407396.1:c.73G>A	NP_001394325.1:p.Gly25Arg	missense
NM_001407397.1:c.73G>A	NP_001394326.1:p.Gly25Arg	missense
NM_001407398.1:c.73G>A	NP_001394327.1:p.Gly25Arg	missense
NM_001407399.1:c.73G>A	NP_001394328.1:p.Gly25Arg	missense
NM_001407400.1:c.73G>A	NP_001394329.1:p.Gly25Arg	missense
NM_001407401.1:c.73G>A	NP_001394330.1:p.Gly25Arg	missense
NC_000003.12:g.15635512G>A
NC_000003.11:g.15677019G>A
NG_008019.2:g.39161G>A
NG_008019.3:g.39162G>A

... more HGVS ... less HGVS

Protein change

G25R

Other names

G45R
p.G45R:GGG>AGG

Canonical SPDI

NC_000003.12:15635511:G:A

Functional consequence Help The effect of the variant on RNA or protein function, based on experimental evidence from submitters.

Global minor allele frequency (GMAF) Help The global minor allele frequency calculated by the 1000 Genomes Project. The minor allele at this location is indicated in parentheses and may be different from the allele represented by this VCV record.

0.00379 (A)

Allele frequency Help The frequency of the allele represented by this VCV record.

NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.01115

1000 Genomes Project 0.00379

Trans-Omics for Precision Medicine (TOPMed) 0.00868

Exome Aggregation Consortium (ExAC) 0.00995

The Genome Aggregation Database (gnomAD), exomes 0.01018

The Genome Aggregation Database (gnomAD) 0.01036

1000 Genomes Project 30x 0.00359

Links

ClinGen: CA241269 dbSNP: rs34885143 VarSome

Genes

Gene	OMIM	ClinGen Gene Dosage Sensitivity Curation		Variation Viewer Help Links to Variation Viewer, a genome browser to view variation data from NCBI databases.	Related variants
Gene	OMIM	HI score Help The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team.	TS score Help The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team.		Within gene Help The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants.	All Help The number of variants in ClinVar for this gene, including smaller variants within the gene and larger CNVs that overlap or fully contain the gene.
BTD		-	-	GRCh38 GRCh37	670	756

Conditions - Germline

Condition Help The condition for this variant-condition (RCV) record in ClinVar.	Classification Help The aggregate germline classification for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to this aggregate classification is shown in parentheses. (# of submissions)	Review status Help The aggregate review status for this variant-condition (RCV) record in ClinVar. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status.	Last evaluated Help The most recent date that a submitter evaluated this variant for the condition.	Variation/condition record Help The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page.
Biotinidase deficiency	Conflicting interpretations of pathogenicity (5)	criteria provided, conflicting classifications	Jan 31, 2024	RCV000021888.20
not specified	Conflicting interpretations of pathogenicity (2)	criteria provided, conflicting classifications	Feb 18, 2022	RCV000185799.15
not provided	Conflicting interpretations of pathogenicity (4)	criteria provided, conflicting classifications	Aug 1, 2024	RCV000724323.30
BTD-related disorder	Benign (1)	no assertion criteria provided	Jan 3, 2024	RCV003974849.2

Submissions - Germline

Classification Help The submitted germline classification for each SCV record. (Last evaluated)	Review status Help Stars represent the review status, or the level of review supporting the submitted (SCV) record. This value is calculated by NCBI based on data from the submitter. Read our rules for calculating the review status. This column also includes a link to the submitter’s assertion criteria if provided, and the collection method. (Assertion criteria)	Condition Help The condition for the classification, provided by the submitter for this submitted (SCV) record. This column also includes the affected status and allele origin of individuals observed with this variant.	Submitter Help The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar.	More information Help This column includes more information supporting the classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter.
Likely benign (Feb 18, 2022)	criteria provided, single submitter (LabCorp Variant Classification Summary - May 2015) Method: clinical testing	not specified Affected status: unknown Allele origin: germline	Women's Health and Genetics/Laboratory Corporation of America, LabCorp Accession: SCV002103646.1 First in ClinVar: Mar 12, 2022 Last updated: Mar 12, 2022
Likely benign (Nov 21, 2020)	criteria provided, single submitter (Quest Diagnostics criteria) Method: clinical testing	not provided Affected status: unknown Allele origin: unknown	Quest Diagnostics Nichols Institute San Juan Capistrano Accession: SCV002047272.2 First in ClinVar: Jan 01, 2022 Last updated: Jan 06, 2024	Publications: PubMed (8) PubMed: 15776412‚ 20556795‚ 15060693‚ 11668630‚ 10400129‚ 28649539‚ 21228398‚ 25087612
Uncertain significance (Feb 08, 2016)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	not specified Affected status: no Allele origin: germline	Genetic Services Laboratory, University of Chicago Accession: SCV000246826.2 First in ClinVar: Oct 05, 2015 Last updated: Nov 10, 2017
Uncertain significance (May 04, 2017)	criteria provided, single submitter (EGL Classification Definitions 2015) Method: clinical testing	not provided Affected status: unknown Allele origin: germline	Eurofins Ntd Llc (ga) Accession: SCV000227009.5 First in ClinVar: Jun 29, 2015 Last updated: Dec 15, 2018	Publications: PubMed (1) PubMed: 15060693 Other databases http://www.egl-eurofins.com/emvc… http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=BTD Number of individuals with the variant: 7 Sex: mixed
Uncertain significance (Apr 01, 2020)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	Biotinidase deficiency Affected status: no Allele origin: paternal	Elsea Laboratory, Baylor College of Medicine Accession: SCV001424288.1 First in ClinVar: Jul 27, 2020 Last updated: Jul 27, 2020	Sex: male Testing laboratory: Org: 1006
Benign (May 03, 2021)	criteria provided, single submitter (GeneDx Variant Classification Process June 2021) Method: clinical testing	Not Provided Affected status: yes Allele origin: germline	GeneDx Accession: SCV000238740.8 First in ClinVar: Jul 18, 2015 Last updated: Mar 04, 2023	Comment: This variant is associated with the following publications: (PMID: 26361991, 12359137, 27329734, 25087612, 21228398, 10400129, 15060693, 15776412, 11668630, 26810761, 16150625, 26990548, 27657684, 31664448)
Likely benign (Jan 31, 2024)	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015)) Method: clinical testing	Biotinidase deficiency Affected status: unknown Allele origin: germline	Labcorp Genetics (formerly Invitae), Labcorp Accession: SCV000630326.5 First in ClinVar: Dec 26, 2017 Last updated: Feb 20, 2024
Likely benign (May 18, 2021)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	Biotinidase deficiency Affected status: no Allele origin: germline	Genome-Nilou Lab Accession: SCV001653479.1 First in ClinVar: Jun 03, 2021 Last updated: Jun 03, 2021	Sex: mixed
Benign (May 04, 2023)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	Biotinidase deficiency Affected status: yes Allele origin: germline	Molecular Genetics, Royal Melbourne Hospital Additional submitter: Shariant Australia, Australian Genomics Accession: SCV004812717.1 First in ClinVar: Apr 15, 2024 Last updated: Apr 15, 2024	Comment: European Non-Finnish population allele frequency is 1.469% (rs34885143, 1052/69016 alleles, 11 homozygotes in gnomAD v3.1). Based on the classification scheme RMH Modified ACMG/AMP Guidelines v1.4.0, … (more) European Non-Finnish population allele frequency is 1.469% (rs34885143, 1052/69016 alleles, 11 homozygotes in gnomAD v3.1). Based on the classification scheme RMH Modified ACMG/AMP Guidelines v1.4.0, this variant is classified as BENIGN. Following criteria are met: BA1 (less)
Benign (Aug 01, 2024)	criteria provided, single submitter (CeGaT Center For Human Genetics Tuebingen Variant Classification Criteria Version 2) Method: clinical testing	not provided Affected status: yes Allele origin: germline	CeGaT Center for Human Genetics Tuebingen Accession: SCV002496789.18 First in ClinVar: Apr 08, 2022 Last updated: Oct 20, 2024	Comment: BTD: BP4, BS1, BS2 Number of individuals with the variant: 33
Benign (Jun 23, 2020)	no assertion criteria provided Method: clinical testing	Biotinidase deficiency Affected status: unknown Allele origin: germline	Natera, Inc. Accession: SCV001454448.1 First in ClinVar: Jan 02, 2021 Last updated: Jan 02, 2021
Benign (Jan 03, 2024)	no assertion criteria provided Method: clinical testing	BTD-related condition Affected status: unknown Allele origin: germline	PreventionGenetics, part of Exact Sciences Accession: SCV004796336.2 First in ClinVar: Mar 16, 2024 Last updated: Oct 08, 2024	Comment: This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).
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Comment:

European Non-Finnish population allele frequency is 1.469% (rs34885143, 1052/69016 alleles, 11 homozygotes in gnomAD v3.1). Based on the classification scheme RMH Modified ACMG/AMP Guidelines v1.4.0, this variant is classified as BENIGN. Following criteria are met: BA1

Germline Functional Evidence

There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar.

Comment:

Citations for germline classification of this variant

Title	Author	Journal	Year	Link
Outcomes of oral biotin treatment in patients with biotinidase deficiency - Twenty years follow-up.	Szymańska E	Molecular genetics and metabolism reports	2015	PMID: 28649539
Pathogenic variants for Mendelian and complex traits in exomes of 6,517 European and African Americans: implications for the return of incidental results.	Tabor HK	American journal of human genetics	2014	PMID: 25087612
Carrier testing for severe childhood recessive diseases by next-generation sequencing.	Bell CJ	Science translational medicine	2011	PMID: 21228398
Analysis of mutations causing biotinidase deficiency.	Pindolia K	Human mutation	2010	PMID: 20556795
Biotinidase deficiency: novel mutations and their biochemical and clinical correlates.	Wolf B	Human mutation	2005	PMID: 15776412
Newborn screening for biotinidase deficiency in Brazil: biochemical and molecular characterizations.	Neto EC	Brazilian journal of medical and biological research = Revista brasileira de pesquisas medicas e biologicas	2004	PMID: 15060693
Mutations in BTD causing biotinidase deficiency.	Hymes J	Human mutation	2001	PMID: 11668630
Mutations causing profound biotinidase deficiency in children ascertained by newborn screening in the United States occur at different frequencies than in symptomatic children.	Norrgard KJ	Pediatric research	1999	PMID: 10400129
http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=BTD	-	-	-	-

Text-mined citations for rs34885143 ...

These citations are identified by LitVar using the rs number, so they may include citations for more than one variant at this location. Please review the LitVar results carefully for your variant of interest.

Record last updated Oct 20, 2024

ClinVar Genomic variation as it relates to human health

NM_001370658.1(BTD):c.73G>A (p.Gly25Arg)

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for rs34885143 ...