7-92447825-T-G

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2BP4_StrongBP6

The NM_021167.5(GATAD1):c.96T>G(p.His32Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000149 in 1,471,886 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. H32Y) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.00097 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000055 ( 1 hom. )

Consequence

GATAD1
NM_021167.5 missense

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:3B:3

Conservation

PhyloP100: 2.34

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 Likely_benign. Variant got -3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.016320169).

BP6

Variant 7-92447825-T-G is Benign according to our data. Variant chr7-92447825-T-G is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 228696.We mark this variant Likely_benign, oryginal submissions are: {Uncertain_significance=3, Likely_benign=3}.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GATAD1	NM_021167.5 linkuse as main transcript	c.96T>G	p.His32Gln	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.96T>G	p.His32Gln	missense_variant	1/5	1	NM_021167.5	P1
GATAD1	ENST00000645746.1 linkuse as main transcript	c.96T>G	p.His32Gln	missense_variant, NMD_transcript_variant	1/6
TMBIM7P	ENST00000641474.1 linkuse as main transcript			upstream_gene_variant
GATAD1	ENST00000644160.1 linkuse as main transcript			upstream_gene_variant

Frequencies

GnomAD3 genomes

AF:

0.000973

AC:

148

AN:

152108

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00345

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000262

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.0000474

AC:

AN:

84424

Hom.:

AF XY:

0.0000212

AC XY:

AN XY:

47160

show subpopulations

Gnomad AFR exome

AF:

0.00138

Gnomad AMR exome

AF:

0.0000734

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000546

AC:

AN:

1319670

Hom.:

Cov.:

AF XY:

0.0000538

AC XY:

AN XY:

650646

show subpopulations

Gnomad4 AFR exome

AF:

0.00237

Gnomad4 AMR exome

AF:

0.000161

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:

0.00

Gnomad4 OTH exome

AF:

0.0000926

GnomAD4 genome

AF:

0.000972

AC:

148

AN:

152216

Hom.:

Cov.:

AF XY:

0.000887

AC XY:

AN XY:

74424

show subpopulations

Gnomad4 AFR

AF:

0.00344

Gnomad4 AMR

AF:

0.000262

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:

0.000473

Alfa

AF:

0.000102

Hom.:

Bravo

AF:

0.000956

ExAC

AF:

0.000115

AC:

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:3Benign:3

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

Dilated cardiomyopathy 2B

Uncertain:1Benign:1

Likely benign, criteria provided, single submitter	clinical testing	Invitae	Dec 04, 2023	- -
Uncertain significance, criteria provided, single submitter	clinical testing	Center for Genomics, Ann and Robert H. Lurie Children's Hospital of Chicago	Mar 30, 2021	GATAD1 NM_021167.4 exon 1 p.His32Gln (c.96T>G): This variant has not been reported in the literature but is present in 0.3% (34/10848) of African alleles in the Genome Aggregation Database (http://gnomad.broadinstitute.org/variant/7-92077139-T-G). This variant is present in ClinVar (Variation ID:228696). Evolutionary conservation for this variant is limited or unavailable; computational predictive tools suggest that this variant may not impact the protein. In summary, data on this variant is insufficient for disease classification. Therefore, the clinical significance of this variant is uncertain. -

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Jan 05, 2015

The p.His32Gln variant in GATAD1 has not been previously reported in individuals with cardiomyopathy, but has been identified in 0.2% (2/1260) of African Americ an chromosomes by the Exome Aggregation Consortium (ExAC, http://exac.broadinsti tute.org; dbSNP rs532003876). Computational prediction tools and conservation an alysis do not provide strong support for or against an impact to the protein. In summary, the clinical significance of the p.His32Gln variant is uncertain. -

Cardiovascular phenotype

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 10, 2023

The p.H32Q variant (also known as c.96T>G), located in coding exon 1 of the GATAD1 gene, results from a T to G substitution at nucleotide position 96. The histidine at codon 32 is replaced by glutamine, an amino acid with highly similar properties. This variant was reported in a sudden death case with limited clinical details provided (Subbotina E et al. Forensic Sci Int, 2018 Dec;293:37-46). This amino acid position is well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. -

GATAD1-related disorder

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Mar 09, 2022

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 08, 2020

This variant is associated with the following publications: (PMID: 30391667) -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.23

BayesDel_noAF

Benign

-0.10

Cadd

Benign

Dann

Benign

0.69

DEOGEN2

Benign

0.0049

Eigen

Benign

-0.62

Eigen_PC

Benign

-0.50

FATHMM_MKL

Benign

0.48

LIST_S2

Benign

0.73

M_CAP

Pathogenic

0.96

MetaRNN

Benign

0.016

MetaSVM

Uncertain

0.71

MutationAssessor

Benign

0.69

MutationTaster

Benign

0.87

PrimateAI

Pathogenic

0.94

PROVEAN

Benign

0.20

REVEL

Uncertain

0.36

Sift

Benign

0.32

Sift4G

Benign

0.56

Polyphen

0.058

Vest4

0.20

MutPred

0.19

Gain of sheet (P = 0.0827);

MVP

0.38

MPC

0.36

ClinPred

0.0067

GERP RS

1.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.055

gMVP

0.13

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