NM_033641.4(COL4A6):c.4243G>A (p.Gly1415Ser) AND not provided

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Mar 8, 2021
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

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:: RCV001930122.6

Allele description [Variation Report for NM_033641.4(COL4A6):c.4243G>A (p.Gly1415Ser)]

NM_033641.4(COL4A6):c.4243G>A (p.Gly1415Ser)

Gene:

COL4A6:collagen type IV alpha 6 chain [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

Xq22.3

Genomic location:

Preferred name:

NM_033641.4(COL4A6):c.4243G>A (p.Gly1415Ser)

HGVS:

NC_000023.11:g.108161709C>T
NG_012059.2:g.282766G>A
NM_001287758.2:c.4294G>A
NM_001287759.2:c.4171G>A
NM_001287760.2:c.4072G>A
NM_001847.4:c.4246G>A
NM_033641.4:c.4243G>AMANE SELECT
NP_001274687.1:p.Gly1432Ser
NP_001274688.1:p.Gly1391Ser
NP_001274689.1:p.Gly1358Ser
NP_001838.2:p.Gly1416Ser
NP_378667.1:p.Gly1415Ser
LRG_233t1:c.4243G>A
LRG_233:g.282766G>A
LRG_233p1:p.Gly1415Ser
NC_000023.10:g.107404939C>T

Protein change:

G1358S

Links:

dbSNP: rs750744219

NCBI 1000 Genomes Browser:

rs750744219

Molecular consequence:

NM_001287758.2:c.4294G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001287759.2:c.4171G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001287760.2:c.4072G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001847.4:c.4246G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_033641.4:c.4243G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002131261	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Mar 8, 2021)	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

SCV002131261

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Mar 8, 2021)

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	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

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV002131261.3

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

Description

This sequence change replaces glycine with serine at codon 1416 of the COL4A6 protein (p.Gly1416Ser). The glycine residue is highly conserved and there is a small physicochemical difference between glycine and serine. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has not been reported in the literature in individuals with COL4A6-related conditions. This variant is present in population databases (rs750744219, ExAC 0.01%). 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.

#	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

Last Updated: Sep 29, 2024

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