chr18-22200758-G-C
Variant summary
Our verdict is Benign. Variant got -7 ACMG points: 0P and 7B. BP4_ModerateBP6BS2
The NM_005257.6(GATA6):āc.1723G>Cā(p.Ala575Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000666 in 1,613,836 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A575S) has been classified as Uncertain significance.
Frequency
Consequence
NM_005257.6 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -7 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
GATA6 | NM_005257.6 | c.1723G>C | p.Ala575Pro | missense_variant | 7/7 | ENST00000269216.10 | |
GATA6 | XM_047437483.1 | c.1723G>C | p.Ala575Pro | missense_variant | 7/7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GATA6 | ENST00000269216.10 | c.1723G>C | p.Ala575Pro | missense_variant | 7/7 | 1 | NM_005257.6 | P1 | |
GATA6 | ENST00000581694.1 | c.1723G>C | p.Ala575Pro | missense_variant | 6/6 | 1 | P1 | ||
ENST00000583442.1 | n.631C>G | non_coding_transcript_exon_variant | 2/2 | 3 |
Frequencies
GnomAD3 genomes AF: 0.000348 AC: 53AN: 152164Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.000541 AC: 136AN: 251198Hom.: 0 AF XY: 0.000515 AC XY: 70AN XY: 135844
GnomAD4 exome AF: 0.000699 AC: 1022AN: 1461672Hom.: 0 Cov.: 31 AF XY: 0.000623 AC XY: 453AN XY: 727130
GnomAD4 genome AF: 0.000348 AC: 53AN: 152164Hom.: 0 Cov.: 33 AF XY: 0.000215 AC XY: 16AN XY: 74330
ClinVar
Submissions by phenotype
not provided Benign:3
Likely benign, criteria provided, single submitter | clinical testing | Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics | Mar 10, 2017 | - - |
Likely benign, no assertion criteria provided | clinical testing | Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+ | - | - - |
Likely benign, no assertion criteria provided | clinical testing | Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC) | - | - - |
Monogenic diabetes Benign:1
Likely benign, criteria provided, single submitter | research | Personalized Diabetes Medicine Program, University of Maryland School of Medicine | Dec 21, 2017 | ACMG criteria: PP3 (6 predictors), BP4 (5 predictors), BS2 (139 hets in gnomAD)=Likely benign - |
GATA6-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | May 02, 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 | Jan 19, 2024 | - - |
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 rs149569288 yet. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at