VCV000224155.6 - ClinVar

NM_014633.5(CTR9):c.1126G>A (p.Glu376Lys)

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.

(3)

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
Pathogenic(1); Likely pathogenic(1); Uncertain significance(1)

criteria provided, conflicting classifications

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

Identifiers

NM_014633.5(CTR9):c.1126G>A (p.Glu376Lys)

Variation ID: 224155 Accession: VCV000224155.6

Type and length

single nucleotide variant, 1 bp

Location

Cytogenetic: 11p15.4 11: 10763811 (GRCh38) [ NCBI UCSC ] 11: 10785358 (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	Mar 12, 2016	Mar 4, 2023	Jul 29, 2022

HGVS

Nucleotide	Protein	Molecular consequence
NM_014633.5:c.1126G>A MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_055448.1:p.Glu376Lys	missense
NM_001346279.2:c.1126G>A	NP_001333208.1:p.Glu376Lys	missense
NM_014633.4:c.1126G>A
NC_000011.10:g.10763811G>A
NC_000011.9:g.10785358G>A
NG_051671.1:g.17825G>A

... more HGVS ... less HGVS

Protein change

E376K

Other names

Canonical SPDI

NC_000011.10:10763810: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.

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

Links

ClinGen: CA354950 dbSNP: rs869312709 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.
CTR9		-	-	GRCh38 GRCh37	524	609
LOC126861140	-	-	-	GRCh38	-	76

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.
not specified	Uncertain significance (1)	criteria provided, single submitter	Jan 14, 2016	RCV000209881.2
CTR9-related neurodevelopmental disorder	Likely pathogenic (1)	criteria provided, single submitter	Apr 1, 2021	RCV001796967.1
not provided	Pathogenic (1)	criteria provided, single submitter	Jul 29, 2022	RCV002272176.2

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 pathogenic (Apr 01, 2021)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: research	CTR9-related neurodevelopmental disorder Affected status: yes Allele origin: de novo	Centre of Medical Genetics, University of Antwerp Accession: SCV001738060.1 First in ClinVar: Dec 23, 2021 Last updated: Dec 23, 2021	Comment: PS2, PM2, PP3 Sex: mixed
Uncertain significance (Jan 14, 2016)	criteria provided, single submitter (HA_assertions_20161101) Method: research	not specified Affected status: yes Allele origin: de novo	HudsonAlpha Institute for Biotechnology, HudsonAlpha Institute for Biotechnology Study: CSER-HudsonAlpha Accession: SCV000265604.4 First in ClinVar: Mar 12, 2016 Last updated: Dec 24, 2022	Number of individuals with the variant: 1 Clinical Features: Intellectual disability, mild (present) , Seizures (present) , Delayed gross motor development (present) , Muscle weakness (present) , Fatigue (present) , Abnormality of the voice … (more) Intellectual disability, mild (present) , Seizures (present) , Delayed gross motor development (present) , Muscle weakness (present) , Fatigue (present) , Abnormality of the voice (present) , Poor coordination (present) (less)
Pathogenic (Jul 29, 2022)	criteria provided, single submitter (GeneDx Variant Classification Process June 2021) Method: clinical testing	Not Provided Affected status: yes Allele origin: germline	GeneDx Accession: SCV002558431.2 First in ClinVar: Aug 08, 2022 Last updated: Mar 04, 2023	Comment: In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Not observed at significant frequency in large population cohorts (gnomAD); … (more) In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 28554332, 35499524) (less)

Comment:

In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 28554332, 35499524)

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

There are no citations for germline classification of this variant in ClinVar. If you know of citations for this variation, please consider submitting that information to ClinVar.

Text-mined citations for rs869312709 ...

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 Mar 26, 2023

ClinVar Genomic variation as it relates to human health

NM_014633.5(CTR9):c.1126G>A (p.Glu376Lys)

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for rs869312709 ...