rs773545065
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 0P and 0B.
The NM_001308093.3(GATA4):c.94G>A(p.Ala32Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000156 in 1,540,244 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A32P) has been classified as Uncertain significance.
Frequency
Consequence
NM_001308093.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
GATA4 | NM_001308093.3 | c.94G>A | p.Ala32Thr | missense_variant | 2/7 | ENST00000532059.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GATA4 | ENST00000532059.6 | c.94G>A | p.Ala32Thr | missense_variant | 2/7 | 1 | NM_001308093.3 | A1 |
Frequencies
GnomAD3 genomes ? AF: 0.00000657 AC: 1AN: 152098Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00000731 AC: 1AN: 136862Hom.: 0 AF XY: 0.0000133 AC XY: 1AN XY: 75224
GnomAD4 exome AF: 0.0000166 AC: 23AN: 1388146Hom.: 0 Cov.: 31 AF XY: 0.0000146 AC XY: 10AN XY: 685662
GnomAD4 genome ? AF: 0.00000657 AC: 1AN: 152098Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74274
ClinVar
Submissions by phenotype
Atrioventricular septal defect 4 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jan 16, 2024 | This sequence change replaces alanine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 32 of the GATA4 protein (p.Ala32Thr). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. 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: 518796). 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. - |
Cardiovascular phenotype Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jun 06, 2016 | The p.A32T variant (also known as c.94G>A), located in coding exon 1 of the GATA4 gene, results from a G to A substitution at nucleotide position 94. The alanine at codon 32 is replaced by threonine, an amino acid with similar properties. Based on data from ExAC, the A allele has an overall frequency of less than 0.01% (1/14019). This variant was not reported in population based cohorts in the following databases: Database of Single Nucleotide Polymorphisms (dbSNP), NHLBI Exome Sequencing Project (ESP), and 1000 Genomes Project. In the ESP, this variant was not observed in 4784 samples (9568 alleles) with coverage at this position. This amino acid position is well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at