rs139637606

Positions:

• chr7-92456514-G-A

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_Strong BP6_Very_Strong BS2

The NM_021167.5(GATAD1):​c.762G>A​(p.Gly254=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00238 in 1,612,746 control chromosomes in the GnomAD database, including 10 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0016 (1 hom., cov: 32)
  • Exomes 𝑓: 0.0025 (9 hom.)
• Consequence: GATAD1 NM_021167.5 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:11
• Conservation: PhyloP100: 2.12

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]

ACMG classification

Verdict is Benign. Variant got -16 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.5).
• BP6: Variant 7-92456514-G-A is Benign according to our data. Variant chr7-92456514-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 137448.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-92456514-G-A is described in Lovd as [Likely_benign]. Variant chr7-92456514-G-A is described in Lovd as [Benign].
• BS2: High Homozygotes in GnomAdExome4 at 9 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GATAD1	NM_021167.5	c.762G>A	p.Gly254=	synonymous_variant	5/5	ENST00000287957.5	NP_066990.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GATAD1	ENST00000287957.5	c.762G>A	p.Gly254=	synonymous_variant	5/5	1	NM_021167.5	ENSP00000287957	P1
GATAD1	ENST00000493878.1	n.1370G>A		non_coding_transcript_exon_variant	3/3	1
GATAD1	ENST00000465247.1	n.774G>A		non_coding_transcript_exon_variant	2/2	2
GATAD1	ENST00000645746.1	c.*353G>A		3_prime_UTR_variant, NMD_transcript_variant	6/6			ENSP00000493785

Frequencies

GnomAD3 genomes AF: 0.00158 AC: 241 AN: 152118 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.000193

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000589

Gnomad ASJ AF: 0.00144

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00394

Gnomad FIN AF: 0.0000942

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00288

Gnomad OTH AF: 0.00143

GnomAD3 exomes AF: 0.00188 AC: 470 AN: 250328 Hom.: 4 AF XY: 0.00195 AC XY: 264 AN XY: 135300

Gnomad AFR exome AF: 0.000555

Gnomad AMR exome AF: 0.000731

Gnomad ASJ exome AF: 0.000698

Gnomad EAS exome AF: 0.0000545

Gnomad SAS exome AF: 0.00415

Gnomad FIN exome AF: 0.000139

Gnomad NFE exome AF: 0.00255

Gnomad OTH exome AF: 0.00164

GnomAD4 exome AF: 0.00246 AC: 3594 AN: 1460510 Hom.: 9 Cov.: 29 AF XY: 0.00248 AC XY: 1804 AN XY: 726562

Gnomad4 AFR exome AF: 0.000569

Gnomad4 AMR exome AF: 0.000607

Gnomad4 ASJ exome AF: 0.00107

Gnomad4 EAS exome AF: 0.0000756

Gnomad4 SAS exome AF: 0.00432

Gnomad4 FIN exome AF: 0.000169

Gnomad4 NFE exome AF: 0.00270

Gnomad4 OTH exome AF: 0.00215

GnomAD4 genome AF: 0.00159 AC: 242 AN: 152236 Hom.: 1 Cov.: 32 AF XY: 0.00160 AC XY: 119 AN XY: 74438

Gnomad4 AFR AF: 0.000193

Gnomad4 AMR AF: 0.000589

Gnomad4 ASJ AF: 0.00144

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00415

Gnomad4 FIN AF: 0.0000942

Gnomad4 NFE AF: 0.00288

Gnomad4 OTH AF: 0.00142

Alfa AF: 0.00229 Hom.: 1

Bravo AF: 0.00139

Asia WGS AF: 0.000577 AC: 2 AN: 3478

EpiCase AF: 0.00284

EpiControl AF: 0.00225

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:11

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Dilated cardiomyopathy 2B Benign:5

Likely benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -
Benign, criteria provided, single submitter	clinical testing	Fulgent Genetics, Fulgent Genetics	Aug 11, 2021	- -
Likely benign, criteria provided, single submitter	clinical testing	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	Mar 02, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 28, 2024	- -
Benign, criteria provided, single submitter	clinical testing	Genome Diagnostics Laboratory, University Medical Center Utrecht	Oct 10, 2014	- -

not specified Benign:3

Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 07, 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. -
Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Mar 19, 2012	p.Gly254Gly in Exon 05 of GATAD1: This variant is not expected to have clinical significance because it does not alter an amino acid residue, is not located wit hin the splice consensus sequence and has been identified in 0.3% (24/7020) of E uropean American chromosomes from a broad population by the NHLBI Exome Sequenci ng Project (http://evs.gs.washington.edu/EVS; dbSNP rs139637606). -
Likely benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Oct 17, 2014	- -

not provided Benign:2

Likely benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -
Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Oct 01, 2022	GATAD1: BP4, BP7 -

Cardiovascular phenotype Benign:1

Benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 18, 2017

This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.50
CADD	Benign	7.3
DANN	Benign	0.65
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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

Other links and lift over

dbSNP: rs139637606; hg19: chr7-92085828;