chr18-22171910-G-T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_005257.6(GATA6):​c.766G>T​(p.Ala256Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000984 in 1,016,296 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A256T) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 9.8e-7 ( 0 hom. )

Consequence

GATA6
NM_005257.6 missense

Scores

2
2
15

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.100

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: Uncertain_significance. The variant received 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.21453291).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
GATA6NM_005257.6 linkc.766G>T p.Ala256Ser missense_variant Exon 2 of 7 ENST00000269216.10 NP_005248.2 Q92908-1
GATA6XM_047437483.1 linkc.766G>T p.Ala256Ser missense_variant Exon 2 of 7 XP_047293439.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
GATA6ENST00000269216.10 linkc.766G>T p.Ala256Ser missense_variant Exon 2 of 7 1 NM_005257.6 ENSP00000269216.3 Q92908-1
GATA6ENST00000581694.1 linkc.766G>T p.Ala256Ser missense_variant Exon 1 of 6 1 ENSP00000462313.1 Q92908-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
9.84e-7
AC:
1
AN:
1016296
Hom.:
0
Cov.:
29
AF XY:
0.00000209
AC XY:
1
AN XY:
478888
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
20498
American (AMR)
AF:
0.00
AC:
0
AN:
6370
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
11342
East Asian (EAS)
AF:
0.00
AC:
0
AN:
20042
South Asian (SAS)
AF:
0.00
AC:
0
AN:
18980
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
18542
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
2548
European-Non Finnish (NFE)
AF:
0.00
AC:
0
AN:
879110
Other (OTH)
AF:
0.0000257
AC:
1
AN:
38864
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.575
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.068
BayesDel_addAF
Benign
-0.051
T
BayesDel_noAF
Benign
-0.31
CADD
Benign
5.6
DANN
Benign
0.87
DEOGEN2
Uncertain
0.62
D;D
Eigen
Benign
-1.3
Eigen_PC
Benign
-1.3
FATHMM_MKL
Benign
0.17
N
LIST_S2
Benign
0.40
.;T
M_CAP
Pathogenic
0.90
D
MetaRNN
Benign
0.21
T;T
MetaSVM
Uncertain
-0.17
T
MutationAssessor
Benign
1.1
L;L
PhyloP100
-0.10
PrimateAI
Pathogenic
0.86
D
PROVEAN
Benign
0.21
N;.
REVEL
Benign
0.21
Sift
Benign
1.0
T;.
Sift4G
Benign
1.0
T;T
Polyphen
0.0
B;B
Vest4
0.074
MutPred
0.39
Gain of glycosylation at A256 (P = 0.0012);Gain of glycosylation at A256 (P = 0.0012);
MVP
0.73
ClinPred
0.067
T
GERP RS
-0.80
Varity_R
0.043
gMVP
0.31
Mutation Taster
=92/8
polymorphism

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: rs1555628783; hg19: chr18-19751871; API