NM_007059.4(KPTN):c.102C>T (p.Gly34=) AND Macrocephaly-developmental delay syndrome

Germline classification:: Conflicting classifications of pathogenicity (2 submissions)
Last evaluated:: Sep 20, 2024
Review status:: criteria provided, conflicting classifications

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV001204463.11

Allele description [Variation Report for NM_007059.4(KPTN):c.102C>T (p.Gly34=)]

NM_007059.4(KPTN):c.102C>T (p.Gly34=)

Gene:

KPTN:kaptin, actin binding protein [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

19q13.32

Genomic location:

Preferred name:

NM_007059.4(KPTN):c.102C>T (p.Gly34=)

HGVS:

NC_000019.10:g.47484059G>A
NG_034097.1:g.5206C>T
NM_001291296.2:c.102C>T
NM_007059.4:c.102C>TMANE SELECT
NP_001278225.1:p.Gly34=
NP_008990.2:p.Gly34=
NC_000019.9:g.47987316G>A
NM_007059.3:c.102C>T
NR_111923.2:n.161C>T

Links:

dbSNP: rs377099246

NCBI 1000 Genomes Browser:

rs377099246

Molecular consequence:

NR_111923.2:n.161C>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NM_001291296.2:c.102C>T - synonymous variant - [Sequence Ontology: SO:0001819]
NM_007059.4:c.102C>T - synonymous variant - [Sequence Ontology: SO:0001819]

Condition(s)

Name:: Macrocephaly-developmental delay syndrome (MRT41)
Synonyms:: INTELLECTUAL DEVELOPMENTAL DISORDER, AUTOSOMAL RECESSIVE 41
Identifiers:: MONDO: MONDO:0014289; MedGen: C3810225; Orphanet: 397612; OMIM: 615637

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001375669	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Nov 7, 2019)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV005328727	3billion	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely benign (Sep 20, 2024)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001375669

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Nov 7, 2019)

germline

clinical testing

PubMed (1)
[See all records that cite this PMID]

SCV005328727

3billion

criteria provided, single submitter

(ACMG Guidelines, 2015)

Likely benign
(Sep 20, 2024)

germline

clinical testing

PubMed (1)
[See all records that cite this PMID]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	no	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group, Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee.

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]

PMID:: 25741868
PMCID:: PMC4544753

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001375669.5

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (1)

Description

In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. This variant has not been reported in the literature in individuals with KPTN-related conditions. This variant is present in population databases (rs377099246, ExAC 0.02%). This sequence change affects codon 34 of the KPTN mRNA. It is a 'silent' change, meaning that it does not change the encoded amino acid sequence of the KPTN protein.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From 3billion, SCV005328727.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (1)

Description

The homozygous variant was found in patients diagnosed with another variant in a different gene, with no symptoms related to the gene containing the homozygous variant.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	no	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Jan 19, 2025

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