rs387906815

Variant names:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_005257.6(GATA6):c.533C>T(p.Ala178Val) variant causes a missense change. The variant allele was found at a frequency of 0.00014 in 1,499,588 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.00082 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000064 ( 2 hom. )

Consequence

GATA6
NM_005257.6 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts P:1B:3

Conservation

PhyloP100: 4.73

Variant links:

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]

GATA6 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0135444105).

BP6

Variant 18-22171677-C-T is Benign according to our data. Variant chr18-22171677-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 30209.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00082 (124/151172) while in subpopulation AFR AF= 0.00285 (118/41340). AF 95% confidence interval is 0.00244. There are 0 homozygotes in gnomad4. There are 49 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd4 at 124 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GATA6	NM_005257.6 link	c.533C>T	p.Ala178Val	missense_variant	Exon 2 of 7	ENST00000269216.10	NP_005248.2	Q92908-1
GATA6	XM_047437483.1 link	c.533C>T	p.Ala178Val	missense_variant	Exon 2 of 7		XP_047293439.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GATA6	ENST00000269216.10 link	c.533C>T	p.Ala178Val	missense_variant	Exon 2 of 7	1	NM_005257.6	ENSP00000269216.3		Q92908-1
GATA6	ENST00000581694.1 link	c.533C>T	p.Ala178Val	missense_variant	Exon 1 of 6	1		ENSP00000462313.1		Q92908-1

Frequencies

GnomAD3 genomes

AF:

0.000821

AC:

124

AN:

151060

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00286

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000197

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000296

Gnomad OTH

AF:

0.000481

GnomAD3 exomes

AF:

0.000180

AC:

AN:

100036

Hom.:

AF XY:

0.000158

AC XY:

AN XY:

56836

show subpopulations

Gnomad AFR exome

AF:

0.00763

Gnomad AMR exome

AF:

0.000114

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000638

AC:

AN:

1348416

Hom.:

Cov.:

AF XY:

0.0000645

AC XY:

AN XY:

666200

show subpopulations

Gnomad4 AFR exome

AF:

0.00272

Gnomad4 AMR exome

AF:

0.0000700

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000188

Gnomad4 OTH exome

AF:

0.000143

GnomAD4 genome

AF:

0.000820

AC:

124

AN:

151172

Hom.:

Cov.:

AF XY:

0.000663

AC XY:

AN XY:

73862

show subpopulations

Gnomad4 AFR

AF:

0.00285

Gnomad4 AMR

AF:

0.000197

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000296

Gnomad4 OTH

AF:

0.000476

Alfa

AF:

0.0455

Hom.:

330

Bravo

AF:

0.000850

ExAC

AF:

0.000321

AC:

ClinVar

Significance: Benign/Likely benign

Submissions summary: Pathogenic:1Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Atrioventricular septal defect 5

Pathogenic:1Benign:1

Jan 14, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Oct 01, 2010

OMIM

Significance: Pathogenic

Review Status: no assertion criteria provided

Collection Method: literature only

- -

Monogenic diabetes

Benign:1

Jan 26, 2018

Personalized Diabetes Medicine Program, University of Maryland School of Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: research

ACMG criteria: PP3 (6 predictors), BP4 (4 predictors), BS1 (1.01% in ExAC African pop.), BS2 (2 homozyotes and 34 hets for dominant condition)=benign -

not provided

Benign:1

Jan 20, 2021

GeneDx

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is associated with the following publications: (PMID: 20581743) -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.20

BayesDel_addAF

Benign

0.011

BayesDel_noAF

Pathogenic

0.25

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.78

D;D

Eigen

Benign

-0.043

Eigen_PC

Benign

-0.17

FATHMM_MKL

Benign

0.62

LIST_S2

Benign

0.59

.;T

MetaRNN

Benign

0.014

T;T

MetaSVM

Uncertain

0.56

MutationAssessor

Benign

0.90

L;L

PrimateAI

Pathogenic

0.92

PROVEAN

Benign

-0.70

N;.

REVEL

Uncertain

0.56

Sift

Uncertain

0.0020

D;.

Sift4G

Uncertain

0.029

D;D

Polyphen

0.99

D;D

Vest4

0.77

MutPred

0.44

Gain of catalytic residue at A178 (P = 0.0275);Gain of catalytic residue at A178 (P = 0.0275);

MVP

0.94

ClinPred

0.18

GERP RS

2.4

Varity_R

0.26

gMVP

0.32

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over