rs34768413

Positions:

chr7-92456449-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_021167.5(GATAD1):c.697C>T(p.Arg233Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0147 in 1,611,378 control chromosomes in the GnomAD database, including 234 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.010 ( 16 hom., cov: 32)

Exomes 𝑓: 0.015 ( 218 hom. )

Consequence

GATAD1
NM_021167.5 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: 1.27

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.008320868).

BP6

Variant 7-92456449-C-T is Benign according to our data. Variant chr7-92456449-C-T is described in ClinVar as [Benign]. Clinvar id is 45829.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-92456449-C-T is described in Lovd as [Benign].

BS1

Variant frequency is greater than expected in population mid. gnomad4_exome allele frequency = 0.0152 (22210/1459056) while in subpopulation MID AF= 0.0193 (111/5766). AF 95% confidence interval is 0.0176. There are 218 homozygotes in gnomad4_exome. There are 11048 alleles in male gnomad4_exome subpopulation. Median coverage is 29. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 16 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GATAD1	NM_021167.5 linkuse as main transcript	c.697C>T	p.Arg233Trp	missense_variant	5/5	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.697C>T	p.Arg233Trp	missense_variant	5/5	1	NM_021167.5	ENSP00000287957	P1
GATAD1	ENST00000493878.1 linkuse as main transcript	n.1305C>T		non_coding_transcript_exon_variant	3/3	1
GATAD1	ENST00000465247.1 linkuse as main transcript	n.709C>T		non_coding_transcript_exon_variant	2/2	2
GATAD1	ENST00000645746.1 linkuse as main transcript	c.*288C>T		3_prime_UTR_variant, NMD_transcript_variant	6/6			ENSP00000493785

Frequencies

GnomAD3 genomes

AF:

0.0100

AC:

1525

AN:

152204

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00241

Gnomad AMI

AF:

0.0395

Gnomad AMR

AF:

0.0101

Gnomad ASJ

AF:

0.00374

Gnomad EAS

AF:

0.000385

Gnomad SAS

AF:

0.00207

Gnomad FIN

AF:

0.0135

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.0152

Gnomad OTH

AF:

0.0120

GnomAD3 exomes

AF:

0.0109

AC:

2734

AN:

251366

Hom.:

AF XY:

0.0114

AC XY:

1542

AN XY:

135854

show subpopulations

Gnomad AFR exome

AF:

0.00215

Gnomad AMR exome

AF:

0.00654

Gnomad ASJ exome

AF:

0.00437

Gnomad EAS exome

AF:

0.000381

Gnomad SAS exome

AF:

0.00346

Gnomad FIN exome

AF:

0.0133

Gnomad NFE exome

AF:

0.0170

Gnomad OTH exome

AF:

0.0148

GnomAD4 exome

AF:

0.0152

AC:

22210

AN:

1459056

Hom.:

218

Cov.:

AF XY:

0.0152

AC XY:

11048

AN XY:

725958

show subpopulations

Gnomad4 AFR exome

AF:

0.00287

Gnomad4 AMR exome

AF:

0.00725

Gnomad4 ASJ exome

AF:

0.00525

Gnomad4 EAS exome

AF:

0.000403

Gnomad4 SAS exome

AF:

0.00339

Gnomad4 FIN exome

AF:

0.0140

Gnomad4 NFE exome

AF:

0.0178

Gnomad4 OTH exome

AF:

0.0129

GnomAD4 genome

AF:

0.0100

AC:

1525

AN:

152322

Hom.:

Cov.:

AF XY:

0.00975

AC XY:

726

AN XY:

74484

show subpopulations

Gnomad4 AFR

AF:

0.00240

Gnomad4 AMR

AF:

0.0101

Gnomad4 ASJ

AF:

0.00374

Gnomad4 EAS

AF:

0.000386

Gnomad4 SAS

AF:

0.00207

Gnomad4 FIN

AF:

0.0135

Gnomad4 NFE

AF:

0.0152

Gnomad4 OTH

AF:

0.0118

Alfa

AF:

0.0155

Hom.:

Bravo

AF:

0.00982

TwinsUK

AF:

0.0181

AC:

ALSPAC

AF:

0.0231

AC:

ESP6500AA

AF:

0.00182

AC:

ESP6500EA

AF:

0.0155

AC:

133

ExAC

AF:

0.0111

AC:

1353

Asia WGS

AF:

0.00318

AC:

AN:

3478

EpiCase

AF:

0.0161

EpiControl

AF:

0.0162

ClinVar

Significance: Benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -
Benign, no assertion criteria provided	clinical testing	Genome Diagnostics Laboratory, University Medical Center Utrecht	-	- -
Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Mar 19, 2012	p.Arg233Trp in Exon 05 of GATAD1: This variant is not expected to have clinical significance because it has been identified in 1.5% (107/7020) of European Ameri can chromosomes from a broad population by the NHLBI Exome Sequencing Project (h ttp://evs.gs.washington.edu/EVS; dbSNP rs34768413). -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jan 17, 2014	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Dilated cardiomyopathy 2B

Benign:2

Benign, criteria provided, single submitter	clinical testing	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	Oct 06, 2023	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Hypertrophic cardiomyopathy 2

Benign:1

Likely benign, no assertion criteria provided

clinical testing

Institute of Human Genetics, University of Wuerzburg

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.22

BayesDel_addAF

Benign

-0.33

BayesDel_noAF

Benign

-0.23

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.20

Eigen

Uncertain

0.29

Eigen_PC

Uncertain

0.25

FATHMM_MKL

Uncertain

0.79

LIST_S2

Uncertain

0.97

MetaRNN

Benign

0.0083

MetaSVM

Benign

-0.81

MutationAssessor

Uncertain

2.2

MutationTaster

Benign

1.0

PrimateAI

Pathogenic

0.81

PROVEAN

Pathogenic

-6.6

REVEL

Benign

0.22

Sift

Uncertain

0.0020

Sift4G

Pathogenic

0.0010

Polyphen

1.0

Vest4

0.061

MPC

0.79

ClinPred

0.057

GERP RS

3.5

Varity_R

0.47

gMVP

0.68

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