18-22171187-G-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_005257.6(GATA6):c.43G>C(p.Gly15Arg) variant causes a missense change. The variant allele was found at a frequency of 0.0066 in 1,599,730 control chromosomes in the GnomAD database, including 299 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin ClinVar.

Frequency

Genomes: 𝑓 0.024 ( 115 hom., cov: 32)

Exomes 𝑓: 0.0048 ( 184 hom. )

Consequence

GATA6
NM_005257.6 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:9

Conservation

PhyloP100: 5.73

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=0.0038214624).

BP6

Variant 18-22171187-G-C is Benign according to our data. Variant chr18-22171187-G-C is described in ClinVar as [Benign]. Clinvar id is 129134.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr18-22171187-G-C is described in Lovd as [Likely_benign]. Variant chr18-22171187-G-C is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0674 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GATA6	NM_005257.6 linkuse as main transcript	c.43G>C	p.Gly15Arg	missense_variant	2/7	ENST00000269216.10
GATA6	XM_047437483.1 linkuse as main transcript	c.43G>C	p.Gly15Arg	missense_variant	2/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GATA6	ENST00000269216.10 linkuse as main transcript	c.43G>C	p.Gly15Arg	missense_variant	2/7	1	NM_005257.6	P1	Q92908-1
GATA6	ENST00000581694.1 linkuse as main transcript	c.43G>C	p.Gly15Arg	missense_variant	1/6	1		P1	Q92908-1

Frequencies

GnomAD3 genomes

AF:

0.0235

AC:

3569

AN:

151908

Hom.:

115

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0696

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0256

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.0466

Gnomad SAS

AF:

0.000831

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000235

Gnomad OTH

AF:

0.0201

GnomAD3 exomes

AF:

0.0139

AC:

3196

AN:

229324

Hom.:

AF XY:

0.0107

AC XY:

1367

AN XY:

127278

show subpopulations

Gnomad AFR exome

AF:

0.0668

Gnomad AMR exome

AF:

0.0399

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0463

Gnomad SAS exome

AF:

0.000330

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000143

Gnomad OTH exome

AF:

0.00965

GnomAD4 exome

AF:

0.00483

AC:

6987

AN:

1447704

Hom.:

184

Cov.:

AF XY:

0.00431

AC XY:

3110

AN XY:

720816

show subpopulations

Gnomad4 AFR exome

AF:

0.0690

Gnomad4 AMR exome

AF:

0.0389

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0570

Gnomad4 SAS exome

AF:

0.000441

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000945

Gnomad4 OTH exome

AF:

0.00858

GnomAD4 genome

AF:

0.0235

AC:

3574

AN:

152026

Hom.:

115

Cov.:

AF XY:

0.0223

AC XY:

1660

AN XY:

74312

show subpopulations

Gnomad4 AFR

AF:

0.0695

Gnomad4 AMR

AF:

0.0258

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.0465

Gnomad4 SAS

AF:

0.000832

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000236

Gnomad4 OTH

AF:

0.0194

Alfa

AF:

0.00275

Hom.:

Bravo

AF:

0.0291

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.0624

AC:

262

ESP6500EA

AF:

0.000483

AC:

ExAC

AF:

0.0127

AC:

1519

EpiCase

AF:

0.000218

EpiControl

AF:

0.000178

ClinVar

Significance: Benign

Submissions summary: Benign:9

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:4

Benign, criteria provided, single submitter	clinical testing	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	Oct 19, 2023	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Sep 06, 2018	- -
Likely benign, no assertion criteria provided	clinical testing	Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	-	- -
Likely benign, no assertion criteria provided	clinical testing	Genome Diagnostics Laboratory, University Medical Center Utrecht	-	- -

not specified

Benign:2

Benign, criteria provided, single submitter	clinical testing	Genetic Services Laboratory, University of Chicago	Mar 05, 2013	- -
Benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -

Monogenic diabetes

Benign:1

Benign, criteria provided, single submitter

research

Personalized Diabetes Medicine Program, University of Maryland School of Medicine

Jan 25, 2019

ACMG criteria: BA1 (6.8% MAF in gnomAD Africans, 4.5% in Asians, 4% in Latinos, overall 1.5%)= benign (REVEL 0.502+3 predictors benign+7 predictors pathogenic= conflicting evidence, not using) -

GATA6-related disorder

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Jul 15, 2019

This variant is classified as 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

Benign, criteria provided, single submitter

clinical testing

Invitae

Feb 01, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.32

BayesDel_addAF

Benign

-0.16

BayesDel_noAF

Uncertain

0.050

Cadd

Pathogenic

Dann

Uncertain

1.0

DEOGEN2

Uncertain

0.53

D;D

Eigen

Uncertain

0.36

Eigen_PC

Uncertain

0.32

FATHMM_MKL

Uncertain

0.88

MetaRNN

Benign

0.0038

T;T

MetaSVM

Uncertain

-0.14

MutationAssessor

Benign

0.81

L;L

MutationTaster

Benign

0.91

N;N

PrimateAI

Uncertain

0.75

PROVEAN

Uncertain

-2.6

D;.

REVEL

Uncertain

0.50

Sift

Pathogenic

0.0

D;.

Sift4G

Uncertain

0.0040

D;D

Polyphen

1.0

D;D

Vest4

0.20

MutPred

0.36

Gain of MoRF binding (P = 0.0104);Gain of MoRF binding (P = 0.0104);

ClinPred

0.039

GERP RS

3.6

Varity_R

0.29

gMVP

0.22

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