NM_001308093.3(GATA4):c.94G>C (p.Ala32Pro) AND Atrioventricular septal defect 4

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: May 23, 2022
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:: RCV002536540.3

Allele description [Variation Report for NM_001308093.3(GATA4):c.94G>C (p.Ala32Pro)]

NM_001308093.3(GATA4):c.94G>C (p.Ala32Pro)

Gene:

GATA4:GATA binding protein 4 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

8p23.1

Genomic location:

Preferred name:

NM_001308093.3(GATA4):c.94G>C (p.Ala32Pro)

HGVS:

NC_000008.11:g.11708406G>C
NG_008177.2:g.36488G>C
NM_001308093.3:c.94G>CMANE SELECT
NM_001308094.2:c.-6+7628G>C
NM_001374273.1:c.-3+4102G>C
NM_001374274.1:c.-3+392G>C
NM_002052.5:c.94G>C
NP_001295022.1:p.Ala32Pro
NP_002043.2:p.Ala32Pro
NC_000008.10:g.11565915G>C
NM_002052.4:c.94G>C

Protein change:

A32P

Links:

dbSNP: rs773545065

NCBI 1000 Genomes Browser:

rs773545065

Molecular consequence:

NM_001308094.2:c.-6+7628G>C - intron variant - [Sequence Ontology: SO:0001627]
NM_001374273.1:c.-3+4102G>C - intron variant - [Sequence Ontology: SO:0001627]
NM_001374274.1:c.-3+392G>C - intron variant - [Sequence Ontology: SO:0001627]
NM_001308093.3:c.94G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_002052.5:c.94G>C - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Atrioventricular septal defect 4 (AVSD4)
Identifiers:: MONDO: MONDO:0013747; MedGen: C3280781; OMIM: 614430

Recent activity

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PI4K2B [Monodelphis domestica]
PI4K2B [Monodelphis domestica]
Gene ID:100013018

Gene
asb16 ankyrin repeat and SOCS box containing 16 [Danio rerio]
asb16 ankyrin repeat and SOCS box containing 16 [Danio rerio]
Gene ID:678621

Gene
txid1035[Organism:exp] AND "type material"[Attribute Name] (4)
BioSample
Homologene neighbors for GEO Profiles (Select 32369186) (0)
GEO Profiles
Homologene neighbors for GEO Profiles (Select 32344331) (0)
GEO Profiles

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV003500605	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (May 23, 2022)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 30755392, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV003500605

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(May 23, 2022)

germline

clinical testing

PubMed (2)
[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

A semiautomated whole-exome sequencing workflow leads to increased diagnostic yield and identification of novel candidate variants.

Ji J, Shen L, Bootwalla M, Quindipan C, Tatarinova T, Maglinte DT, Buckley J, Raca G, Saitta SC, Biegel JA, Gai X.

Cold Spring Harb Mol Case Stud. 2019 Apr 1;5(2). doi:pii: a003756. 10.1101/mcs.a003756. Print 2019 Apr.

PubMed [citation]

PMID:: 30755392
PMCID:: PMC6549575

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, SCV003500605.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

Description

This sequence change replaces alanine, which is neutral and non-polar, with proline, which is neutral and non-polar, at codon 32 of the GATA4 protein (p.Ala32Pro). 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 missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). ClinVar contains an entry for this variant (Variation ID: 599008). This missense change has been observed in individual(s) with clinical features of GATA4-related conditions (PMID: 30755392). This variant is present in population databases (no rsID available, gnomAD 0.01%).

#	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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