rs564747350

Positions:

Variant summary

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

The ENST00000287957.5(GATAD1):c.604G>A(p.Ala202Thr) variant causes a missense change. The variant allele was found at a frequency of 0.0000798 in 1,591,894 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 (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A202P) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.00015 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000072 ( 0 hom. )

Consequence

GATAD1
ENST00000287957.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, multiple submitters, no conflicts U:5

Conservation

PhyloP100: 4.70

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 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=0.094615966).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GATAD1	NM_021167.5 linkuse as main transcript	c.604G>A	p.Ala202Thr	missense_variant	4/5	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.604G>A	p.Ala202Thr	missense_variant	4/5	1	NM_021167.5	ENSP00000287957	P1
GATAD1	ENST00000493878.1 linkuse as main transcript	n.1212G>A		non_coding_transcript_exon_variant	2/3	1
GATAD1	ENST00000465247.1 linkuse as main transcript	n.616G>A		non_coding_transcript_exon_variant	1/2	2
GATAD1	ENST00000645746.1 linkuse as main transcript	c.*195G>A		3_prime_UTR_variant, NMD_transcript_variant	5/6			ENSP00000493785

Frequencies

GnomAD3 genomes

AF:

0.000151

AC:

AN:

152054

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000578

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000189

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000235

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000126

AC:

AN:

230628

Hom.:

AF XY:

0.000120

AC XY:

AN XY:

124592

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.000543

Gnomad EAS exome

AF:

0.000405

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000424

Gnomad NFE exome

AF:

0.0000744

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000722

AC:

104

AN:

1439722

Hom.:

Cov.:

AF XY:

0.0000727

AC XY:

AN XY:

715260

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.000512

Gnomad4 EAS exome

AF:

0.000102

Gnomad4 SAS exome

AF:

0.0000123

Gnomad4 FIN exome

AF:

0.000413

Gnomad4 NFE exome

AF:

0.0000535

Gnomad4 OTH exome

AF:

0.0000839

GnomAD4 genome

AF:

0.000151

AC:

AN:

152172

Hom.:

Cov.:

AF XY:

0.000148

AC XY:

AN XY:

74384

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000579

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000189

Gnomad4 NFE

AF:

0.000235

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.000215

Hom.:

Bravo

AF:

0.0000718

ExAC

AF:

0.000107

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Dilated cardiomyopathy 2B

Uncertain:3

Uncertain significance, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 10, 2023	This sequence change replaces alanine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 202 of the GATAD1 protein (p.Ala202Thr). This variant is present in population databases (rs564747350, gnomAD 0.05%). This variant has not been reported in the literature in individuals affected with GATAD1-related conditions. ClinVar contains an entry for this variant (Variation ID: 163499). 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 with a negative predictive value of 80%. 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. -
Uncertain significance, criteria provided, single submitter	clinical testing	New York Genome Center	Jun 19, 2020	- -
Uncertain significance, criteria provided, single submitter	clinical testing	Fulgent Genetics, Fulgent Genetics	Jul 23, 2021	- -

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

May 15, 2014

The Ala202Thr variant in GATAD1 has not been previously reported in individuals with cardiomyopathy or in large population studies. Computational prediction too ls and conservation analysis do not provide strong support for or against an imp act to the protein. In summary, the clinical significance of the Ala202Thr varia nt is uncertain. -

Cardiovascular phenotype

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 18, 2024

The p.A202T variant (also known as c.604G>A), located in coding exon 4 of the GATAD1 gene, results from a G to A substitution at nucleotide position 604. The alanine at codon 202 is replaced by threonine, an amino acid with similar properties. This amino acid position is not 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. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.24

BayesDel_addAF

Benign

-0.23

BayesDel_noAF

Benign

-0.18

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.12

Eigen

Uncertain

0.29

Eigen_PC

Uncertain

0.36

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.93

M_CAP

Benign

0.060

MetaRNN

Benign

0.095

MetaSVM

Uncertain

0.12

MutationAssessor

Benign

1.5

MutationTaster

Benign

0.94

PrimateAI

Benign

0.43

PROVEAN

Benign

-2.4

REVEL

Uncertain

0.33

Sift

Benign

0.10

Sift4G

Uncertain

0.028

Polyphen

0.89

Vest4

0.46

MVP

0.57

MPC

0.35

ClinPred

0.067

GERP RS

4.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.072

gMVP

0.23

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