8-11750126-G-C
Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4BS2
The NM_001308093.3(GATA4):āc.802G>Cā(p.Val268Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000867 in 1,614,022 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ā ).
Frequency
Consequence
NM_001308093.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -5 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152280Hom.: 0 Cov.: 34
GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251224Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135848
GnomAD4 exome AF: 0.00000889 AC: 13AN: 1461742Hom.: 0 Cov.: 32 AF XY: 0.0000124 AC XY: 9AN XY: 727190
GnomAD4 genome AF: 0.00000657 AC: 1AN: 152280Hom.: 0 Cov.: 34 AF XY: 0.00 AC XY: 0AN XY: 74398
ClinVar
Submissions by phenotype
Atrioventricular septal defect 4 Uncertain:1
This sequence change replaces valine, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 267 of the GATA4 protein (p.Val267Leu). This variant is present in population databases (no rsID available, gnomAD 0.0009%). This variant has not been reported in the literature in individuals affected with GATA4-related conditions. ClinVar contains an entry for this variant (Variation ID: 1321571). 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 not expected to disrupt GATA4 protein function with a negative predictive value of 80%. 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. -
not provided Uncertain:1
Has not been previously published as pathogenic or benign to our knowledge; Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis indicates that this missense variant does not alter protein structure/function -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at