GeneBe

18-22171651-C-T

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2BP4_ModerateBP6_ModerateBP7

The NM_005257.6(GATA6):​c.507C>T​(p.Phe169Phe) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000659 in 151,688 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 0.0000066 ( 0 hom., cov: 32)

Consequence

GATA6
NM_005257.6 synonymous

Scores

1
1

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.65

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

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -3 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.35).
BP6
Variant 18-22171651-C-T is Benign according to our data. Variant chr18-22171651-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 1978462.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
Synonymous conserved (PhyloP=1.65 with no splicing effect.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
GATA6NM_005257.6 linkc.507C>T p.Phe169Phe synonymous_variant Exon 2 of 7 ENST00000269216.10 NP_005248.2 Q92908-1
GATA6XM_047437483.1 linkc.507C>T p.Phe169Phe synonymous_variant Exon 2 of 7 XP_047293439.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
GATA6ENST00000269216.10 linkc.507C>T p.Phe169Phe synonymous_variant Exon 2 of 7 1 NM_005257.6 ENSP00000269216.3 Q92908-1
GATA6ENST00000581694.1 linkc.507C>T p.Phe169Phe synonymous_variant Exon 1 of 6 1 ENSP00000462313.1 Q92908-1

Frequencies

GnomAD3 genomes
AF:
0.00000659
AC:
1
AN:
151688
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000242
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:
0.00
Gnomad OTH
AF:
0.00
GnomAD4 exome
Cov.:
31
GnomAD4 genome
AF:
0.00000659
AC:
1
AN:
151688
Hom.:
0
Cov.:
32
AF XY:
0.0000135
AC XY:
1
AN XY:
74040
show subpopulations
African (AFR)
AF:
0.0000242
AC:
1
AN:
41384
American (AMR)
AF:
0.00
AC:
0
AN:
15242
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
3466
East Asian (EAS)
AF:
0.00
AC:
0
AN:
5088
South Asian (SAS)
AF:
0.00
AC:
0
AN:
4822
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
10476
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
314
European-Non Finnish (NFE)
AF:
0.00
AC:
0
AN:
67896
Other (OTH)
AF:
0.00
AC:
0
AN:
2088
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.475
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Alfa
AF:
0.0000712
Hom.:
0
Bravo
AF:
0.0000151

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

Atrioventricular septal defect 5 Benign:1
Jan 22, 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
-0.35
CADD
Benign
13
DANN
Uncertain
0.98
PhyloP100
1.6

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

Other links and lift over

dbSNP: rs980861173; hg19: chr18-19751612; API