NM_000091.5(COL4A3):c.4045G>A (p.Gly1349Ser) AND not provided

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Mar 23, 2023
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:: RCV001069634.6

Allele description [Variation Report for NM_000091.5(COL4A3):c.4045G>A (p.Gly1349Ser)]

NM_000091.5(COL4A3):c.4045G>A (p.Gly1349Ser)

Genes:

MFF-DT:MFF divergent transcript [Gene - HGNC]
COL4A3:collagen type IV alpha 3 chain [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

2q36.3

Genomic location:

Preferred name:

NM_000091.5(COL4A3):c.4045G>A (p.Gly1349Ser)

HGVS:

NC_000002.12:g.227304036G>A
NG_011591.1:g.144472G>A
NM_000091.5:c.4045G>AMANE SELECT
NP_000082.2:p.Gly1349Ser
LRG_230t1:c.4045G>A
LRG_230:g.144472G>A
NC_000002.11:g.228168752G>A
NM_000091.4:c.4045G>A

Protein change:

G1349S

Links:

dbSNP: rs2073401281

NCBI 1000 Genomes Browser:

rs2073401281

Molecular consequence:

NM_000091.5:c.4045G>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
SCV001234813	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Mar 23, 2023)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 33369211, 33532864, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001234813

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Mar 23, 2023)

germline

clinical testing

PubMed (3)
[See all records that cite these PMIDs]

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

Deciphering the pathogenesis of the COL4-related hematuric nephritis: A genotype/phenotype study.

Uliana V, Sebastio P, Riva M, Carli D, Ruberto C, Bianchi L, Graziano C, Capelli I, Faletra F, Pillon R, Mattina T, Sensi A, Bonatti F, Percesepe A.

Mol Genet Genomic Med. 2021 Feb;9(2):e1576. doi: 10.1002/mgg3.1576. Epub 2020 Dec 24.

PubMed [citation]

PMID:: 33369211
PMCID:: PMC8077073

Clinical utility of genetic testing in early-onset kidney disease: seven genes are the main players.

Domingo-Gallego A, Pybus M, Bullich G, Furlano M, Ejarque-Vila L, Lorente-Grandoso L, Ruiz P, Fraga G, López González M, Piñero-Fernández JA, Rodríguez-Peña L, Llano-Rivas I, Sáez R, Bujons-Tur A, Ariceta G, Guirado L, Torra R, Ars E.

Nephrol Dial Transplant. 2022 Mar 25;37(4):687-696. doi: 10.1093/ndt/gfab019.

PubMed [citation]

PMID:: 33532864

See all PubMed Citations (3)

Details of each submission

From Invitae, SCV001234813.5

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

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 disrupt the consensus splice site. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt COL4A3 protein function. ClinVar contains an entry for this variant (Variation ID: 862824). This missense change has been observed in individual(s) with COL4A3-related conditions (PMID: 33369211, 33532864). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces glycine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 1349 of the COL4A3 protein (p.Gly1349Ser).

#	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: Feb 28, 2024

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