chr8-11708320-A-C
Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2
The NM_001308093.3(GATA4):āc.8A>Cā(p.Gln3Pro) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000265 in 1,584,238 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (ā ā ). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. Q3E) has been classified as Uncertain significance.
Frequency
Consequence
NM_001308093.3 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Likely_benign. Variant got -4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
GATA4 | NM_001308093.3 | c.8A>C | p.Gln3Pro | missense_variant | 2/7 | ENST00000532059.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GATA4 | ENST00000532059.6 | c.8A>C | p.Gln3Pro | missense_variant | 2/7 | 1 | NM_001308093.3 | A1 |
Frequencies
GnomAD3 genomes AF: 0.000171 AC: 26AN: 152146Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000399 AC: 8AN: 200394Hom.: 0 AF XY: 0.0000270 AC XY: 3AN XY: 111028
GnomAD4 exome AF: 0.0000112 AC: 16AN: 1431976Hom.: 0 Cov.: 31 AF XY: 0.00000422 AC XY: 3AN XY: 711294
GnomAD4 genome AF: 0.000171 AC: 26AN: 152262Hom.: 0 Cov.: 32 AF XY: 0.000161 AC XY: 12AN XY: 74456
ClinVar
Submissions by phenotype
Atrioventricular septal defect 4 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jan 05, 2024 | This sequence change replaces glutamine, which is neutral and polar, with proline, which is neutral and non-polar, at codon 3 of the GATA4 protein (p.Gln3Pro). This variant is present in population databases (rs374132087, gnomAD 0.06%), and has an allele count higher than expected for a pathogenic variant. 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: 472782). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. 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
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Jul 03, 2023 | In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Not observed among 157 patients with congenital heart disease, but was observed in an unaffected control (Schluterman et al., 2007); This variant is associated with the following publications: (PMID: 17352393) - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at