rs531449433

Positions:

• chr7-92447905-G-C

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 2P and 12B. PM2 BP4_Strong BP6_Very_Strong

The ENST00000287957.5(GATAD1):​c.176G>C​(p.Gly59Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000326 in 1,255,810 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0017 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00014 (1 hom.)
• Consequence: GATAD1 ENST00000287957.5 missense
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 3.53

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 -10 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.008299649).
• BP6: Variant 7-92447905-G-C is Benign according to our data. Variant chr7-92447905-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 163496.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GATAD1	NM_021167.5	c.176G>C	p.Gly59Ala	missense_variant	1/5	ENST00000287957.5	NP_066990.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GATAD1	ENST00000287957.5	c.176G>C	p.Gly59Ala	missense_variant	1/5	1	NM_021167.5	ENSP00000287957	P1
GATAD1	ENST00000644160.1	n.32G>C		non_coding_transcript_exon_variant	1/2
GATAD1	ENST00000645746.1	c.176G>C	p.Gly59Ala	missense_variant, NMD_transcript_variant	1/6			ENSP00000493785

Frequencies

GnomAD3 genomes AF: 0.00168 AC: 256 AN: 151966 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00572

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000721

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: 0.0000294

Gnomad OTH AF: 0.00287

GnomAD4 exome AF: 0.000138 AC: 152 AN: 1103736 Hom.: 1 Cov.: 32 AF XY: 0.000135 AC XY: 71 AN XY: 526828

Gnomad4 AFR exome AF: 0.00508

Gnomad4 AMR exome AF: 0.000615

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000432

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000750

Gnomad4 OTH exome AF: 0.000545

GnomAD4 genome AF: 0.00169 AC: 257 AN: 152074 Hom.: 0 Cov.: 33 AF XY: 0.00160 AC XY: 119 AN XY: 74370

Gnomad4 AFR AF: 0.00573

Gnomad4 AMR AF: 0.000720

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000294

Gnomad4 OTH AF: 0.00284

Alfa AF: 0.000971 Hom.: 0

Bravo AF: 0.00200

ClinVar

Significance: Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Feb 22, 2017

p.Gly59Ala in exon 1 of GATAD1: This variant is not expected to have clinical si gnificance because it has been identified in 1.1% (12/1106) of African chromosom es by the 1000 Genomes Project (dbSNP rs531449433). -

Dilated cardiomyopathy 2B Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 30, 2024

- -

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 20, 2021

- -

Cardiovascular phenotype Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 26, 2018

This alteration is classified as likely 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
AlphaMissense	Benign	0.077
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.17
CADD	Benign	19
DANN	Benign	0.52
DEOGEN2	Benign	0.0046	T
Eigen	Benign	-0.52
Eigen_PC	Benign	-0.42
FATHMM_MKL	Benign	0.36	N
LIST_S2	Benign	0.40	T
M_CAP	Pathogenic	0.84	D
MetaRNN	Benign	0.0083	T
MetaSVM	Benign	-0.69	T
MutationAssessor	Benign	0.0	N
MutationTaster	Benign	1.0	N
PrimateAI	Pathogenic	0.88	D
PROVEAN	Benign	-0.010	N
REVEL	Benign	0.28
Sift	Benign	0.40	T
Sift4G	Uncertain	0.012	D
Polyphen		0.0	B
Vest4		0.16
MutPred		0.14		Gain of helix (P = 0.0854);
MVP		0.38
MPC		0.34
ClinPred		0.15	T
GERP RS		2.5
Varity_R		0.082
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

Other links and lift over

dbSNP: rs531449433; hg19: chr7-92077219;