Genetic Variant GATA6:c.1302+831G>T (chr18-22177952-G-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_005257.6(GATA6):c.1302+831G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.19 ( 2424 hom., cov: 16)

Consequence

GATA6
NM_005257.6 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -3.41

Publications

1 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:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.95).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.507 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GATA6	NM_005257.6 link	c.1302+831G>T		intron_variant	Intron 3 of 6	ENST00000269216.10	NP_005248.2	Q92908-1
GATA6	XM_047437483.1 link	c.1302+831G>T		intron_variant	Intron 3 of 6		XP_047293439.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GATA6	ENST00000269216.10 link	c.1302+831G>T		intron_variant	Intron 3 of 6	1	NM_005257.6	ENSP00000269216.3		Q92908-1
GATA6	ENST00000581694.1 link	c.1302+831G>T		intron_variant	Intron 2 of 5	1		ENSP00000462313.1		Q92908-1

Frequencies

GnomAD3 genomes

AF:

0.188

AC:

14664

AN:

77886

Hom.:

2409

Cov.:

show subpopulations

Gnomad AFR

AF:

0.515

Gnomad AMI

AF:

0.0189

Gnomad AMR

AF:

0.185

Gnomad ASJ

AF:

0.0697

Gnomad EAS

AF:

0.105

Gnomad SAS

AF:

0.131

Gnomad FIN

AF:

0.0485

Gnomad MID

AF:

0.117

Gnomad NFE

AF:

0.0462

Gnomad OTH

AF:

0.171

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.189

AC:

14705

AN:

77924

Hom.:

2424

Cov.:

AF XY:

0.194

AC XY:

7211

AN XY:

37148

show subpopulations

African (AFR)

AF:

0.516

AC:

10433

AN:

20236

American (AMR)

AF:

0.187

AC:

1431

AN:

7670

Ashkenazi Jewish (ASJ)

AF:

0.0697

AC:

140

AN:

2010

East Asian (EAS)

AF:

0.105

AC:

290

AN:

2762

South Asian (SAS)

AF:

0.130

AC:

287

AN:

2208

European-Finnish (FIN)

AF:

0.0485

AC:

187

AN:

3858

Middle Eastern (MID)

AF:

0.123

AC:

AN:

114

European-Non Finnish (NFE)

AF:

0.0463

AC:

1734

AN:

37486

Other (OTH)

AF:

0.170

AC:

179

AN:

1050

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.470

Heterozygous variant carriers

336

673

1009

1346

1682

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

138

276

414

552

690

<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.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.95

CADD

Benign

1.1

(source)

DANN

Benign

0.34

PhyloP100

-3.4

Mutation Taster

=100/0

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over