rs151176879
Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 2P and 7B. PM1BP4_ModerateBP6BS2
The NM_005257.6(GATA6):c.1375G>A(p.Ala459Thr) variant causes a missense change. The variant allele was found at a frequency of 0.000151 in 1,614,158 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 Conflicting classifications of pathogenicity (no stars). Synonymous variant affecting the same amino acid position (i.e. A459A) has been classified as Likely benign.
Frequency
Consequence
NM_005257.6 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -5 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
GATA6 | NM_005257.6 | c.1375G>A | p.Ala459Thr | missense_variant | 4/7 | ENST00000269216.10 | |
GATA6 | XM_047437483.1 | c.1375G>A | p.Ala459Thr | missense_variant | 4/7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GATA6 | ENST00000269216.10 | c.1375G>A | p.Ala459Thr | missense_variant | 4/7 | 1 | NM_005257.6 | P1 | |
GATA6 | ENST00000581694.1 | c.1375G>A | p.Ala459Thr | missense_variant | 3/6 | 1 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.000815 AC: 124AN: 152170Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000183 AC: 46AN: 251490Hom.: 0 AF XY: 0.000162 AC XY: 22AN XY: 135920
GnomAD4 exome AF: 0.0000821 AC: 120AN: 1461872Hom.: 0 Cov.: 31 AF XY: 0.0000715 AC XY: 52AN XY: 727236
GnomAD4 genome ? AF: 0.000814 AC: 124AN: 152286Hom.: 0 Cov.: 32 AF XY: 0.000940 AC XY: 70AN XY: 74482
ClinVar
Submissions by phenotype
not provided Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Feb 04, 2021 | Has not been reported as pathogenic or benign in association with arrhythmia to our knowledge; Reported in ClinVar (ClinVar Variant ID# 211064; Landrum et al., 2016); In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; This variant is associated with the following publications: (PMID: 25107291) - |
Uncertain significance, criteria provided, single submitter | clinical testing | Revvity Omics, Revvity | Feb 08, 2022 | - - |
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Jun 27, 2014 | - - |
Monogenic diabetes Uncertain:1
Uncertain significance, criteria provided, single submitter | research | Personalized Diabetes Medicine Program, University of Maryland School of Medicine | Jun 29, 2018 | ACMG criteria: PP3 (8 predictors, REVEL = 0.687; not using BP4 (3 predictors)), PM1 (located in second zinc finger domain, lots of other mutations present (PMID: 22158542)), BS2 (77 individuals in gnomAD (69 (0.28%) African) = VUS. Variant in paper showing family members of probands with mutations/early onset severe phenotype and variable expressivity (some with just diabetes, PMID: 23223019, 24310933) - |
GATA6-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Feb 18, 2022 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Atrioventricular septal defect 5 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Dec 16, 2023 | - - |
Pancreatic hypoplasia-diabetes-congenital heart disease syndrome Other:1
Uncertain risk allele, criteria provided, single submitter | research | Clinical Genomics, Uppaluri K&H Personalized Medicine Clinic | - | Potent mutations in GATA6 gene are associated with neonatal diabetes, decreased insulin production due to pancreatic aplasia or hypoplasia. Also associated with isolated cardiac abnormalities in children, like atrial septal defects.However no sufficient evidence is found to ascertain the role of this particular variant rs151176879 yet. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at