NM_005257.6:c.237G>C

Variant names:

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP6_Very_StrongBP7

The NM_005257.6(GATA6):c.237G>C(p.Leu79Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000111 in 1,587,192 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 0.00018 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00010 ( 0 hom. )

Consequence

GATA6
NM_005257.6 synonymous

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 3.04

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 -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.55).

BP6

Variant 18-22171381-G-C is Benign according to our data. Variant chr18-22171381-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 412721.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=3.04 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GATA6	NM_005257.6 link	c.237G>C	p.Leu79Leu	synonymous_variant	Exon 2 of 7	ENST00000269216.10	NP_005248.2	Q92908-1
GATA6	XM_047437483.1 link	c.237G>C	p.Leu79Leu	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.237G>C	p.Leu79Leu	synonymous_variant	Exon 2 of 7	1	NM_005257.6	ENSP00000269216.3		Q92908-1
GATA6	ENST00000581694.1 link	c.237G>C	p.Leu79Leu	synonymous_variant	Exon 1 of 6	1		ENSP00000462313.1		Q92908-1

Frequencies

GnomAD3 genomes

AF:

0.000185

AC:

AN:

151666

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000485

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000262

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0000944

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000309

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000103

AC:

AN:

203726

AF XY:

0.0000879

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000308

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000998

Gnomad NFE exome

AF:

0.000188

Gnomad OTH exome

AF:

0.000382

GnomAD4 exome

AF:

0.000103

AC:

148

AN:

1435526

Hom.:

Cov.:

AF XY:

0.0000981

AC XY:

AN XY:

713616

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33222

American (AMR)

AF:

0.0000230

AC:

AN:

43490

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25824

East Asian (EAS)

AF:

0.00

AC:

AN:

39156

South Asian (SAS)

AF:

0.00

AC:

AN:

84800

European-Finnish (FIN)

AF:

0.0000542

AC:

AN:

36910

Middle Eastern (MID)

AF:

0.000178

AC:

AN:

5630

European-Non Finnish (NFE)

AF:

0.000124

AC:

137

AN:

1106782

Other (OTH)

AF:

0.000117

AC:

AN:

59712

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

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:

0.000185

AC:

AN:

151666

Hom.:

Cov.:

AF XY:

0.000243

AC XY:

AN XY:

74068

show subpopulations

African (AFR)

AF:

0.0000485

AC:

AN:

41262

American (AMR)

AF:

0.000262

AC:

AN:

15262

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3466

East Asian (EAS)

AF:

0.00

AC:

AN:

5106

South Asian (SAS)

AF:

0.00

AC:

AN:

4796

European-Finnish (FIN)

AF:

0.0000944

AC:

AN:

10588

Middle Eastern (MID)

AF:

0.00

AC:

AN:

306

European-Non Finnish (NFE)

AF:

0.000309

AC:

AN:

67886

Other (OTH)

AF:

0.00

AC:

AN:

2082

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.493

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:

0.000262

Hom.:

Bravo

AF:

0.000136

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:1

May 26, 2021

GeneDx

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Atrioventricular septal defect 5

Benign:1

Jan 26, 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

-0.55

CADD

Benign

6.6

(source)

DANN

Benign

0.89

PhyloP100

3.0

PromoterAI

-0.021

Neutral

(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