rs143026087
Positions:
Variant summary
Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2
The NM_005257.6(GATA6):c.1374C>T(p.Asn458=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00393 in 1,614,158 control chromosomes in the GnomAD database, including 26 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.0023 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0041 ( 26 hom. )
Consequence
GATA6
NM_005257.6 synonymous
NM_005257.6 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.761
Genes affected
GATA6 (HGNC:4174): (GATA binding protein 6) This gene is a member of a small family of zinc finger transcription factors that play an important role in the regulation of cellular differentiation and organogenesis during vertebrate development. This gene is expressed during early embryogenesis and localizes to endo- and mesodermally derived cells during later embryogenesis and thereby plays an important role in gut, lung, and heart development. Mutations in this gene are associated with several congenital defects. [provided by RefSeq, Mar 2012]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -17 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.59).
BP6
?
Variant 18-22181524-C-T is Benign according to our data. Variant chr18-22181524-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 240127.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr18-22181524-C-T is described in Lovd as [Likely_benign]. Variant chr18-22181524-C-T is described in Lovd as [Benign].
BP7
?
Synonymous conserved (PhyloP=-0.761 with no splicing effect.
BS2
?
High AC in GnomAd4 at 353 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
GATA6 | NM_005257.6 | c.1374C>T | p.Asn458= | synonymous_variant | 4/7 | ENST00000269216.10 | |
GATA6 | XM_047437483.1 | c.1374C>T | p.Asn458= | synonymous_variant | 4/7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GATA6 | ENST00000269216.10 | c.1374C>T | p.Asn458= | synonymous_variant | 4/7 | 1 | NM_005257.6 | P1 | |
GATA6 | ENST00000581694.1 | c.1374C>T | p.Asn458= | synonymous_variant | 3/6 | 1 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00232 AC: 353AN: 152180Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.00217 AC: 546AN: 251484Hom.: 3 AF XY: 0.00246 AC XY: 334AN XY: 135916
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GnomAD4 exome AF: 0.00410 AC: 5991AN: 1461860Hom.: 26 Cov.: 32 AF XY: 0.00407 AC XY: 2963AN XY: 727228
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GnomAD4 genome ? AF: 0.00232 AC: 353AN: 152298Hom.: 0 Cov.: 32 AF XY: 0.00226 AC XY: 168AN XY: 74482
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:9
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:3
Benign, no assertion criteria provided | clinical testing | Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+ | - | - - |
Benign, no assertion criteria provided | clinical testing | Genome Diagnostics Laboratory, University Medical Center Utrecht | - | - - |
Likely benign, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Apr 05, 2017 | - - |
not provided Benign:3
Benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Feb 01, 2024 | GATA6: BP4, BP7, BS1, BS2 - |
Likely benign, no assertion criteria provided | clinical testing | Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC) | - | - - |
Benign, criteria provided, single submitter | clinical testing | ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories | Nov 01, 2023 | - - |
Tetralogy of Fallot;C1857586:Conotruncal heart malformations;C3280939:Atrioventricular septal defect 5;C3280943:Atrial septal defect 9;C4012454:Pancreatic hypoplasia-diabetes-congenital heart disease syndrome Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Sep 28, 2021 | - - |
Inborn genetic diseases Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Jun 16, 2023 | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
Atrioventricular septal defect 5 Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 25, 2024 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at