rs368297251
Positions:
Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4BS2
The NM_005257.6(GATA6):c.352C>T(p.Leu118Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000431 in 1,602,262 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).
Frequency
Genomes: 𝑓 0.00028 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000018 ( 0 hom. )
Consequence
GATA6
NM_005257.6 missense
NM_005257.6 missense
Scores
3
8
7
Clinical Significance
Conservation
PhyloP100: 3.39
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]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -5 ACMG points.
BP4
?
Computational evidence support a benign effect (MetaRNN=0.33969793).
BS2
?
High AC in GnomAd4 at 43 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
GATA6 | NM_005257.6 | c.352C>T | p.Leu118Phe | missense_variant | 2/7 | ENST00000269216.10 | |
GATA6 | XM_047437483.1 | c.352C>T | p.Leu118Phe | missense_variant | 2/7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GATA6 | ENST00000269216.10 | c.352C>T | p.Leu118Phe | missense_variant | 2/7 | 1 | NM_005257.6 | P1 | |
GATA6 | ENST00000581694.1 | c.352C>T | p.Leu118Phe | missense_variant | 1/6 | 1 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.000283 AC: 43AN: 152118Hom.: 0 Cov.: 32
GnomAD3 genomes
?
AF:
AC:
43
AN:
152118
Hom.:
Cov.:
32
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD3 exomes AF: 0.0000570 AC: 13AN: 227976Hom.: 0 AF XY: 0.0000631 AC XY: 8AN XY: 126820
GnomAD3 exomes
AF:
AC:
13
AN:
227976
Hom.:
AF XY:
AC XY:
8
AN XY:
126820
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad SAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.0000179 AC: 26AN: 1450036Hom.: 0 Cov.: 31 AF XY: 0.0000139 AC XY: 10AN XY: 721814
GnomAD4 exome
AF:
AC:
26
AN:
1450036
Hom.:
Cov.:
31
AF XY:
AC XY:
10
AN XY:
721814
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome ? AF: 0.000282 AC: 43AN: 152226Hom.: 0 Cov.: 32 AF XY: 0.000323 AC XY: 24AN XY: 74414
GnomAD4 genome
?
AF:
AC:
43
AN:
152226
Hom.:
Cov.:
32
AF XY:
AC XY:
24
AN XY:
74414
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
Bravo
AF:
ESP6500AA
AF:
AC:
2
ESP6500EA
AF:
AC:
0
ExAC
?
AF:
AC:
6
ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:2Benign:1Other:1
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
Monogenic diabetes Uncertain:1
Uncertain significance, criteria provided, single submitter | research | Personalized Diabetes Medicine Program, University of Maryland School of Medicine | Sep 07, 2018 | ACMG criteria: N/A (REVEL 0.595 + PP3/8 predictors + BP4/2 predictors= conflicting evidence, not using)=VUS - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Dec 08, 2020 | Has not been previously published as pathogenic or benign to our knowledge; Reported in ClinVar (ClinVar Variant ID# 572520; Landrum et al., 2016); In silico analysis supports that this missense variant does not alter protein structure/function - |
Atrioventricular septal defect 5 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Dec 11, 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 rs368297251 yet. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
BayesDel_addAF
Benign
T
BayesDel_noAF
Uncertain
CADD
Uncertain
DANN
Uncertain
DEOGEN2
Uncertain
D;D
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Benign
D
M_CAP
Pathogenic
D
MetaRNN
Benign
T;T
MetaSVM
Pathogenic
D
MutationAssessor
Benign
L;L
MutationTaster
Benign
D;D
PrimateAI
Pathogenic
D
PROVEAN
Benign
N;.
REVEL
Uncertain
Sift
Uncertain
D;.
Sift4G
Benign
T;T
Polyphen
D;D
Vest4
MVP
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at