rs587777710

Positions:

• chr18-22171856-G-A
• chr18-22171856-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The ENST00000269216.10(GATA6):​c.712G>A​(p.Gly238Arg) variant causes a missense change. The variant allele was found at a frequency of 0.000000964 in 1,037,674 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. G238G) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 9.6e-7 (0 hom.)
• Consequence: GATA6 ENST00000269216.10 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.93

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GATA6	NM_005257.6	c.712G>A	p.Gly238Arg	missense_variant	2/7	ENST00000269216.10	NP_005248.2
GATA6	XM_047437483.1	c.712G>A	p.Gly238Arg	missense_variant	2/7		XP_047293439.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GATA6	ENST00000269216.10	c.712G>A	p.Gly238Arg	missense_variant	2/7	1	NM_005257.6	ENSP00000269216	P1
GATA6	ENST00000581694.1	c.712G>A	p.Gly238Arg	missense_variant	1/6	1		ENSP00000462313	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 9.64e-7 AC: 1 AN: 1037674 Hom.: 0 Cov.: 29 AF XY: 0.00000204 AC XY: 1 AN XY: 489678

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000112

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Mar 01, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.44
BayesDel_addAF	Uncertain	0.13	D
BayesDel_noAF	Uncertain	-0.050
CADD	Uncertain	25
DANN	Uncertain	0.98
DEOGEN2	Pathogenic	0.82	D;D
Eigen	Benign	-0.72
Eigen_PC	Benign	-0.78
FATHMM_MKL	Benign	0.75	D
LIST_S2	Benign	0.56	.;T
M_CAP	Pathogenic	0.94	D
MetaRNN	Uncertain	0.50	D;D
MetaSVM	Uncertain	0.18	D
MutationAssessor	Uncertain	2.2	M;M
MutationTaster	Benign	1.0	D;D
PrimateAI	Pathogenic	0.96	D
PROVEAN	Benign	-1.2	N;.
REVEL	Uncertain	0.40
Sift	Uncertain	0.0010	D;.
Sift4G	Benign	0.12	T;T
Polyphen		0.0030	B;B
Vest4		0.45
MutPred		0.41		Gain of methylation at G238 (P = 0.0059);Gain of methylation at G238 (P = 0.0059);
MVP		0.87
ClinPred		0.92	D
GERP RS		0.29
Varity_R		0.23
gMVP		0.61

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

LitVar

Other links and lift over

dbSNP: rs587777710; hg19: chr18-19751817;