chr18-22171999-G-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS1

The NM_005257.6(GATA6):c.855G>T(p.Ala285Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000925 in 1,231,450 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 Likely benign (★★).

Frequency

Genomes: 𝑓 0.00059 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00097 ( 0 hom. )

Consequence

GATA6
NM_005257.6 synonymous

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: -0.362

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -17 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BP6

Variant 18-22171999-G-T is Benign according to our data. Variant chr18-22171999-G-T is described in ClinVar as Likely_benign. ClinVar VariationId is 472918.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.362 with no splicing effect.

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.000595 (90/151360) while in subpopulation NFE AF = 0.000828 (56/67666). AF 95% confidence interval is 0.000654. There are 0 homozygotes in GnomAd4. There are 37 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GATA6	NM_005257.6 link	c.855G>T	p.Ala285Ala	synonymous_variant	Exon 2 of 7	ENST00000269216.10	NP_005248.2	Q92908-1
GATA6	XM_047437483.1 link	c.855G>T	p.Ala285Ala	synonymous_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.855G>T	p.Ala285Ala	synonymous_variant	Exon 2 of 7	1	NM_005257.6	ENSP00000269216.3		Q92908-1
GATA6	ENST00000581694.1 link	c.855G>T	p.Ala285Ala	synonymous_variant	Exon 1 of 6	1		ENSP00000462313.1		Q92908-1

Frequencies

GnomAD3 genomes

AF:

0.000595

AC:

AN:

151254

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000726

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000526

Gnomad ASJ

AF:

0.00578

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000827

Gnomad OTH

AF:

0.00144

GnomAD2 exomes

AF:

0.00

AC:

AN:

326

AF XY:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000971

AC:

1049

AN:

1080090

Hom.:

Cov.:

AF XY:

0.00100

AC XY:

511

AN XY:

510790

show subpopulations

African (AFR)

AF:

0.000133

AC:

AN:

22634

American (AMR)

AF:

0.000366

AC:

AN:

8188

Ashkenazi Jewish (ASJ)

AF:

0.00560

AC:

AN:

14116

East Asian (EAS)

AF:

0.00

AC:

AN:

26060

South Asian (SAS)

AF:

0.0000995

AC:

AN:

20092

European-Finnish (FIN)

AF:

0.00

AC:

AN:

21262

Middle Eastern (MID)

AF:

0.00541

AC:

AN:

2958

European-Non Finnish (NFE)

AF:

0.000975

AC:

898

AN:

921308

Other (OTH)

AF:

0.00110

AC:

AN:

43472

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.513

Heterozygous variant carriers

143

215

286

358

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

132

176

220

<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:

0.000595

AC:

AN:

151360

Hom.:

Cov.:

AF XY:

0.000500

AC XY:

AN XY:

73944

show subpopulations

African (AFR)

AF:

0.0000724

AC:

AN:

41442

American (AMR)

AF:

0.000526

AC:

AN:

15216

Ashkenazi Jewish (ASJ)

AF:

0.00578

AC:

AN:

3462

East Asian (EAS)

AF:

0.00

AC:

AN:

5100

South Asian (SAS)

AF:

0.00

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10342

Middle Eastern (MID)

AF:

0.00

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.000828

AC:

AN:

67666

Other (OTH)

AF:

0.00143

AC:

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

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:

0.000476

Hom.:

Bravo

AF:

0.000740

ClinVar

Significance: Likely benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:5

Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Aug 31, 2021

GeneDx

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Genome Diagnostics Laboratory, University Medical Center Utrecht

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Mar 01, 2023

CeGaT Center for Human Genetics Tuebingen

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

GATA6: BP4, BP7 -

Breakthrough Genomics, Breakthrough Genomics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

GATA6-related disorder

Benign:1

Jan 02, 2020

PreventionGenetics, part of Exact Sciences

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

This variant is classified as likely 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

Jan 21, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

1.0

(source)

DANN

Benign

0.69

PhyloP100

-0.36

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

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over