chr18-22172001-G-A

Variant names:

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_005257.6(GATA6):c.857G>A(p.Gly286Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000114 in 1,232,984 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★★).

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000092 ( 0 hom. )

Consequence

GATA6
NM_005257.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, multiple submitters, no conflicts U:2

Conservation

PhyloP100: 3.29

Publications

0 publications found

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 Gene-Disease associations (from GenCC):

atrial septal defect 9
Inheritance: AD Classification: DEFINITIVE, LIMITED Submitted by: G2P, Ambry Genetics
atrioventricular septal defect 5
Inheritance: AD Classification: DEFINITIVE, LIMITED Submitted by: G2P, Labcorp Genetics (formerly Invitae)
GATA6-related congenital heart disease with or without pancreatic agenesis or neonatal diabetes
Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
pancreatic hypoplasia-diabetes-congenital heart disease syndrome
Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, Genomics England PanelApp, Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae)
metabolic syndrome
Inheritance: AD Classification: STRONG Submitted by: Genomics England PanelApp
neonatal diabetes mellitus
Inheritance: AD Classification: STRONG Submitted by: Genomics England PanelApp
tetralogy of fallot
Inheritance: AD Classification: MODERATE Submitted by: Ambry Genetics
familial atrial fibrillation
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
conotruncal heart malformations
Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

GATA6 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005257.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GATA6	NM_005257.6	MANE Select	c.857G>A	p.Gly286Asp	missense	Exon 2 of 7	NP_005248.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GATA6	ENST00000269216.10	TSL:1 MANE Select	c.857G>A	p.Gly286Asp	missense	Exon 2 of 7	ENSP00000269216.3
	GATA6	ENST00000581694.1	TSL:1	c.857G>A	p.Gly286Asp	missense	Exon 1 of 6	ENSP00000462313.1

Frequencies

GnomAD3 genomes

AF:

0.0000265

AC:

AN:

151206

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.0000591

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000924

AC:

AN:

1081778

Hom.:

Cov.:

AF XY:

0.00000977

AC XY:

AN XY:

511718

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

22652

American (AMR)

AF:

0.00

AC:

AN:

8224

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

14170

East Asian (EAS)

AF:

0.00

AC:

AN:

26168

South Asian (SAS)

AF:

0.00

AC:

AN:

20276

European-Finnish (FIN)

AF:

0.00

AC:

AN:

21302

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2966

European-Non Finnish (NFE)

AF:

0.0000108

AC:

AN:

922448

Other (OTH)

AF:

0.00

AC:

AN:

43572

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000265

AC:

AN:

151206

Hom.:

Cov.:

AF XY:

0.0000136

AC XY:

AN XY:

73798

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41302

American (AMR)

AF:

0.00

AC:

AN:

15190

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3462

East Asian (EAS)

AF:

0.00

AC:

AN:

5102

South Asian (SAS)

AF:

0.00

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10342

Middle Eastern (MID)

AF:

0.00

AC:

AN:

312

European-Non Finnish (NFE)

AF:

0.0000591

AC:

AN:

67678

Other (OTH)

AF:

0.00

AC:

AN:

2074

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.488

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000151

ClinVar

ClinVar submissions as Germline

Significance:Uncertain significance

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

Atrioventricular septal defect 5 (1)

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.34

BayesDel_addAF

Uncertain

0.14

BayesDel_noAF

Uncertain

-0.040

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.75

Eigen

Benign

-0.54

Eigen_PC

Benign

-0.70

FATHMM_MKL

Benign

0.27

LIST_S2

Benign

0.48

M_CAP

Pathogenic

0.97

MetaRNN

Uncertain

0.45

MetaSVM

Uncertain

0.21

MutationAssessor

Benign

1.7

PhyloP100

3.3

PrimateAI

Pathogenic

0.91

PROVEAN

Benign

-0.69

REVEL

Uncertain

0.41

Sift

Benign

0.068

Sift4G

Benign

0.41

Polyphen

0.89

Vest4

0.28

MutPred

0.38

Loss of catalytic residue at A285 (P = 0.1144)

MVP

0.92

ClinPred

0.54

GERP RS

1.8

Varity_R

0.067

gMVP

0.31

Mutation Taster

=86/14

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

ClinVar submissions as Germline

Computational scores

Splicing

Publications

Other links and lift over