Variant 7-92447760-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The ENST00000287957.5(GATAD1):c.31G>A(p.Val11Ile) variant causes a missense change. The variant allele was found at a frequency of 0.00000371 in 1,346,720 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000037 ( 0 hom. )

Consequence

GATAD1
ENST00000287957.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.63

Variant links:

Genes affected

GATAD1 (HGNC:29941): (GATA zinc finger domain containing 1) The protein encoded by this gene contains a zinc finger at the N-terminus, and is thought to bind to a histone modification site that regulates gene expression. Mutations in this gene have been associated with autosomal recessive dilated cardiomyopathy. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Jun 2012]

GATAD1 links:

TMBIM7P (HGNC:49212): (transmembrane BAX inhibitor motif containing 7, pseudogene)

TMBIM7P links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.25206363).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GATAD1	NM_021167.5 linkuse as main transcript	c.31G>A	p.Val11Ile	missense_variant	1/5	ENST00000287957.5	NP_066990.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
GATAD1	ENST00000287957.5 linkuse as main transcript	c.31G>A	p.Val11Ile	missense_variant	1/5	1	NM_021167.5	ENSP00000287957	P1
TMBIM7P	ENST00000641474.1 linkuse as main transcript	n.54C>T		non_coding_transcript_exon_variant	1/10
GATAD1	ENST00000645746.1 linkuse as main transcript	c.31G>A	p.Val11Ile	missense_variant, NMD_transcript_variant	1/6			ENSP00000493785

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000371

AC:

AN:

1346720

Hom.:

Cov.:

AF XY:

0.00000301

AC XY:

AN XY:

664318

show subpopulations

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:

0.0000133

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000284

Gnomad4 OTH exome

AF:

0.0000181

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Cardiovascular phenotype

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 13, 2021

The p.V11I variant (also known as c.31G>A), located in coding exon 1 of the GATAD1 gene, results from a G to A substitution at nucleotide position 31. The valine at codon 11 is replaced by isoleucine, an amino acid with highly similar properties. This amino acid position is well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.091

BayesDel_addAF

Benign

-0.019

BayesDel_noAF

Benign

-0.26

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.014

Eigen

Benign

-0.49

Eigen_PC

Benign

-0.36

FATHMM_MKL

Benign

0.61

LIST_S2

Benign

0.83

M_CAP

Pathogenic

0.96

MetaRNN

Benign

0.25

MetaSVM

Pathogenic

0.82

MutationAssessor

Benign

0.81

MutationTaster

Benign

0.62

PrimateAI

Pathogenic

0.81

PROVEAN

Benign

-0.40

REVEL

Uncertain

0.35

Sift

Benign

0.20

Sift4G

Benign

0.53

Polyphen

0.0

Vest4

0.21

MutPred

0.21

Loss of catalytic residue at V11 (P = 0.0424);

MVP

0.21

MPC

0.31

ClinPred

0.27

GERP RS

2.6

Varity_R

0.038

gMVP

0.11

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over