Variant 7-92447767-A-G details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_021167.5(GATAD1):c.38A>G(p.Lys13Arg) variant causes a missense change. The variant allele was found at a frequency of 0.00000267 in 1,499,362 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: 𝑓 0.0000066 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000022 ( 0 hom. )

Consequence

GATAD1
NM_021167.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.92

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:

Genome browser will be placed here

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=0.248483).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GATAD1	NM_021167.5 linkuse as main transcript	c.38A>G	p.Lys13Arg	missense_variant	1/5	ENST00000287957.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
GATAD1	ENST00000287957.5 linkuse as main transcript	c.38A>G	p.Lys13Arg	missense_variant	1/5	1	NM_021167.5	P1
TMBIM7P	ENST00000641474.1 linkuse as main transcript	n.47T>C		non_coding_transcript_exon_variant	1/10
GATAD1	ENST00000645746.1 linkuse as main transcript	c.38A>G	p.Lys13Arg	missense_variant, NMD_transcript_variant	1/6

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000223

AC:

AN:

1347070

Hom.:

Cov.:

AF XY:

0.00000452

AC XY:

AN XY:

664360

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:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.47e-7

Gnomad4 OTH exome

AF:

0.0000361

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152292

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74480

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Asia WGS

AF:

0.000578

AC:

AN:

3476

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Dilated cardiomyopathy 2B

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Invitae

Sep 12, 2022

In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt GATAD1 protein function. This variant has not been reported in the literature in individuals affected with GATAD1-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces lysine, which is basic and polar, with arginine, which is basic and polar, at codon 13 of the GATAD1 protein (p.Lys13Arg). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.070

BayesDel_addAF

Benign

-0.0030

BayesDel_noAF

Benign

-0.24

Cadd

Benign

Dann

Uncertain

0.98

DEOGEN2

Benign

0.015

Eigen

Benign

-0.62

Eigen_PC

Benign

-0.54

FATHMM_MKL

Benign

0.41

LIST_S2

Benign

0.71

M_CAP

Pathogenic

0.98

MetaRNN

Benign

0.25

MetaSVM

Uncertain

0.64

MutationAssessor

Benign

1.7

MutationTaster

Benign

0.96

PrimateAI

Pathogenic

0.86

PROVEAN

Benign

-1.3

REVEL

Uncertain

0.38

Sift

Benign

0.18

Sift4G

Benign

0.38

Polyphen

0.0

Vest4

0.14

MutPred

0.34

Loss of methylation at K13 (P = 0.0021);

MVP

0.45

MPC

0.27

ClinPred

0.53

GERP RS

0.27

Varity_R

0.089

gMVP

0.17

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