NM_021167.5:c.62A>G

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_021167.5(GATAD1):c.62A>G(p.Lys21Arg) variant causes a missense change. The variant allele was found at a frequency of 0.00000521 in 1,344,524 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 (★★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000052 ( 0 hom. )

Consequence

GATAD1
NM_021167.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, multiple submitters, no conflicts U:2

Conservation

PhyloP100: 4.71

Publications

0 publications found

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 Gene-Disease associations (from GenCC):

familial isolated dilated cardiomyopathy
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
dilated cardiomyopathy
Inheritance: AR Classification: LIMITED Submitted by: ClinGen
dilated cardiomyopathy 2B
Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)

GATAD1 links:

TMBIM7P (HGNC:):

TMBIM7P links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.17456245).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GATAD1	NM_021167.5 link	c.62A>G	p.Lys21Arg	missense_variant	Exon 1 of 5	ENST00000287957.5	NP_066990.3	Q8WUU5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
GATAD1	ENST00000287957.5 link	c.62A>G	p.Lys21Arg	missense_variant	Exon 1 of 5	1	NM_021167.5	ENSP00000287957.3	Q8WUU5
TMBIM7P	ENST00000641474.1 link	n.23T>C		non_coding_transcript_exon_variant	Exon 1 of 10
GATAD1	ENST00000645746.1 link	n.62A>G		non_coding_transcript_exon_variant	Exon 1 of 6			ENSP00000493785.1	A0A2R8Y4H1
GATAD1	ENST00000644160.1 link	n.-83A>G		upstream_gene_variant

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000521

AC:

AN:

1344524

Hom.:

Cov.:

AF XY:

0.00000452

AC XY:

AN XY:

663148

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

26866

American (AMR)

AF:

0.0000352

AC:

AN:

28402

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

23500

East Asian (EAS)

AF:

0.00

AC:

AN:

28326

South Asian (SAS)

AF:

0.00

AC:

AN:

74794

European-Finnish (FIN)

AF:

0.00

AC:

AN:

47230

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5560

European-Non Finnish (NFE)

AF:

0.00000569

AC:

AN:

1054550

Other (OTH)

AF:

0.00

AC:

AN:

55296

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Dilated cardiomyopathy 2B

Uncertain:1

Feb 25, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This sequence change replaces lysine, which is basic and polar, with arginine, which is basic and polar, at codon 21 of the GATAD1 protein (p.Lys21Arg). This variant is not present in population databases (gnomAD no frequency). 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: 1752705). 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. -

Cardiovascular phenotype

Uncertain:1

Aug 19, 2024

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The p.K21R variant (also known as c.62A>G), located in coding exon 1 of the GATAD1 gene, results from an A to G substitution at nucleotide position 62. The lysine at codon 21 is replaced by arginine, an amino acid with highly similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. 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

0.082

BayesDel_addAF

Benign

0.0090

BayesDel_noAF

Benign

-0.22

CADD

Benign

(source)

DANN

Benign

0.64

DEOGEN2

Benign

0.0011

Eigen

Benign

-0.77

Eigen_PC

Benign

-0.56

FATHMM_MKL

Benign

0.69

LIST_S2

Benign

0.79

M_CAP

Pathogenic

0.98

MetaRNN

Benign

0.17

MetaSVM

Uncertain

-0.21

MutationAssessor

Benign

-0.36

PhyloP100

4.7

PrimateAI

Pathogenic

0.93

PROVEAN

Benign

0.75

REVEL

Uncertain

0.32

Sift

Benign

1.0

Sift4G

Benign

0.85

Polyphen

0.0010

Vest4

0.18

MutPred

0.26

Loss of methylation at K21 (P = 0.0111);

MVP

0.30

MPC

0.25

ClinPred

0.067

GERP RS

3.3

PromoterAI

-0.0046

Neutral

(source)

Varity_R

0.049

gMVP

0.24

Mutation Taster

=72/28

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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NM_021167.5:c.62A>G

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over