chr18-22171169-T-A

Position:

• chr18-22171169-T-A

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4 BS2

The NM_005257.6(GATA6):​c.25T>A​(p.Cys9Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000414 in 1,447,694 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 Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000041 (0 hom.)
• Consequence: GATA6 NM_005257.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.89

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 Likely_benign. Variant got -5 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.37768647).
• BS2: High AC in GnomAdExome4 at 6 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GATA6	NM_005257.6	c.25T>A	p.Cys9Ser	missense_variant	2/7	ENST00000269216.10	NP_005248.2
GATA6	XM_047437483.1	c.25T>A	p.Cys9Ser	missense_variant	2/7		XP_047293439.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GATA6	ENST00000269216.10	c.25T>A	p.Cys9Ser	missense_variant	2/7	1	NM_005257.6	ENSP00000269216	P1
GATA6	ENST00000581694.1	c.25T>A	p.Cys9Ser	missense_variant	1/6	1		ENSP00000462313	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000414 AC: 6 AN: 1447694 Hom.: 0 Cov.: 31 AF XY: 0.00000277 AC XY: 2 AN XY: 720754

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: 0.00000540

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 specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Genetic Services Laboratory, University of Chicago

Oct 13, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Uncertain	0.053	T
BayesDel_noAF	Benign	-0.16
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.55	D;D
Eigen	Benign	-0.40
Eigen_PC	Benign	-0.28
FATHMM_MKL	Uncertain	0.85	D
LIST_S2	Benign	0.50	.;T
M_CAP	Pathogenic	0.47	D
MetaRNN	Benign	0.38	T;T
MetaSVM	Uncertain	0.65	D
MutationAssessor	Benign	0.81	L;L
MutationTaster	Benign	0.69	N;N
PrimateAI	Uncertain	0.61	T
PROVEAN	Uncertain	-3.1	D;.
REVEL	Uncertain	0.37
Sift	Benign	0.039	D;.
Sift4G	Benign	0.34	T;T
Polyphen		0.0040	B;B
Vest4		0.22
MutPred		0.33		Loss of catalytic residue at C9 (P = 0.0052);Loss of catalytic residue at C9 (P = 0.0052);
MVP		0.90
ClinPred		0.79	D
GERP RS		2.3
Varity_R		0.25
gMVP		0.27

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr18-19751130;