chr8-11708331-A-G
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Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PP3_ModerateBS2
The NM_001308093.3(GATA4):āc.19A>Gā(p.Met7Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000489 in 1,432,050 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ).
Frequency
Genomes: not found (cov: 32)
Exomes š: 0.0000049 ( 0 hom. )
Consequence
GATA4
NM_001308093.3 missense
NM_001308093.3 missense
Scores
5
6
2
Clinical Significance
Conservation
PhyloP100: 3.42
Genes affected
GATA4 (HGNC:4173): (GATA binding protein 4) This gene encodes a member of the GATA family of zinc-finger transcription factors. Members of this family recognize the GATA motif which is present in the promoters of many genes. This protein is thought to regulate genes involved in embryogenesis and in myocardial differentiation and function, and is necessary for normal testicular development. Mutations in this gene have been associated with cardiac septal defects. Additionally, alterations in gene expression have been associated with several cancer types. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Apr 2015]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -2 ACMG points.
PP3
MetaRNN computational evidence supports a deleterious effect, 0.844
BS2
High AC in GnomAdExome4 at 7 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
GATA4 | NM_001308093.3 | c.19A>G | p.Met7Val | missense_variant | 2/7 | ENST00000532059.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GATA4 | ENST00000532059.6 | c.19A>G | p.Met7Val | missense_variant | 2/7 | 1 | NM_001308093.3 | A1 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 genomes
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32
GnomAD3 exomes AF: 0.0000150 AC: 3AN: 200506Hom.: 0 AF XY: 0.0000180 AC XY: 2AN XY: 111224
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GnomAD4 exome AF: 0.00000489 AC: 7AN: 1432050Hom.: 0 Cov.: 31 AF XY: 0.00000562 AC XY: 4AN XY: 711434
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GnomAD4 genome Cov.: 32
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32
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Atrioventricular septal defect 4 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Oct 25, 2022 | 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: "Possibly Damaging"; Align-GVGD: "Class C0"). ClinVar contains an entry for this variant (Variation ID: 846765). This variant has not been reported in the literature in individuals affected with GATA4-related conditions. This variant is present in population databases (no rsID available, gnomAD 0.01%). This sequence change replaces methionine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 7 of the GATA4 protein (p.Met7Val). - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Uncertain
D
BayesDel_noAF
Pathogenic
CADD
Uncertain
DANN
Uncertain
DEOGEN2
Uncertain
T;.;D;.;.
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
M_CAP
Pathogenic
D
MetaRNN
Pathogenic
D;D;D;D;D
MetaSVM
Pathogenic
D
MutationTaster
Benign
D;D;D
PrimateAI
Pathogenic
D
Polyphen
0.96
.;.;D;.;.
Vest4
0.60, 0.65
MutPred
Gain of catalytic residue at M7 (P = 0.0766);Gain of catalytic residue at M7 (P = 0.0766);Gain of catalytic residue at M7 (P = 0.0766);Gain of catalytic residue at M7 (P = 0.0766);Gain of catalytic residue at M7 (P = 0.0766);
MVP
MPC
0.041
ClinPred
D
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at