rs1291588606

Variant names:

• chr7-92447760-G-A
• rs1291588606
• NM_021167.5:c.31G>A

Your query was ambiguous. Multiple possible variants found:

• chr7-92447760-G-A
• chr7-92447760-G-T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_021167.5(GATAD1):​c.31G>A​(p.Val11Ile) variant causes a missense change. The variant allele was found at a frequency of 0.00000371 in 1,346,720 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 (★). Synonymous variant affecting the same amino acid position (i.e. V11V) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000037 (0 hom.)
• Consequence: GATAD1 NM_021167.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.63
• Publications: 0 publications found

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)

TMBIM7P (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.25206363).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GATAD1	NM_021167.5	c.31G>A	p.Val11Ile	missense_variant	Exon 1 of 5	ENST00000287957.5	NP_066990.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GATAD1	ENST00000287957.5	c.31G>A	p.Val11Ile	missense_variant	Exon 1 of 5	1	NM_021167.5	ENSP00000287957.3
TMBIM7P	ENST00000641474.1	n.54C>T		non_coding_transcript_exon_variant	Exon 1 of 10
GATAD1	ENST00000645746.1	n.31G>A		non_coding_transcript_exon_variant	Exon 1 of 6			ENSP00000493785.1
GATAD1	ENST00000644160.1	n.-114G>A		upstream_gene_variant

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00 AC: 0 AN: 97682 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000371 AC: 5 AN: 1346720 Hom.: 0 Cov.: 31 AF XY: 0.00000301 AC XY: 2 AN XY: 664318

African (AFR) AF: 0.00 AC: 0 AN: 26864

American (AMR) AF: 0.00 AC: 0 AN: 28910

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23496

East Asian (EAS) AF: 0.00 AC: 0 AN: 28480

South Asian (SAS) AF: 0.0000133 AC: 1 AN: 75172

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 47228

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5552

European-Non Finnish (NFE) AF: 0.00000284 AC: 3 AN: 1055630

Other (OTH) AF: 0.0000181 AC: 1 AN: 55388

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Cardiovascular phenotype Uncertain:1

May 06, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The p.V11I variant (also known as c.31G>A), located in coding exon 1 of the GATAD1 gene, results from a G to A substitution at nucleotide position 31. The valine at codon 11 is replaced by isoleucine, an amino acid with highly similar properties. This amino acid position is well 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	0.091
BayesDel_addAF	Benign	-0.019	T
BayesDel_noAF	Benign	-0.26
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.014	T
Eigen	Benign	-0.49
Eigen_PC	Benign	-0.36
FATHMM_MKL	Benign	0.61	D
LIST_S2	Benign	0.83	T
M_CAP	Pathogenic	0.96	D
MetaRNN	Benign	0.25	T
MetaSVM	Pathogenic	0.82	D
MutationAssessor	Benign	0.81	L
PhyloP100		3.6
PrimateAI	Pathogenic	0.81	D
PROVEAN	Benign	-0.40	N
REVEL	Uncertain	0.35
Sift	Benign	0.20	T
Sift4G	Benign	0.53	T
Polyphen		0.0	B
Vest4		0.21
MutPred		0.21		Loss of catalytic residue at V11 (P = 0.0424);
MVP		0.21
MPC		0.31
ClinPred		0.27	T
GERP RS		2.6
PromoterAI		-0.071	Neutral
Varity_R		0.038
gMVP		0.11
Mutation Taster		=95/5	polymorphism

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

Other links and lift over

dbSNP: rs1291588606; hg19: chr7-92077074;