7-92447760-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 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. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• 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

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]

TMBIM7P (HGNC:49212): (transmembrane BAX inhibitor motif containing 7, pseudogene)

ACMG classification

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=0.25206363).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GATAD1	NM_021167.5	c.31G>A	p.Val11Ile	missense_variant	1/5	ENST00000287957.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GATAD1	ENST00000287957.5	c.31G>A	p.Val11Ile	missense_variant	1/5	1	NM_021167.5	P1
TMBIM7P	ENST00000641474.1	n.54C>T		non_coding_transcript_exon_variant	1/10
GATAD1	ENST00000645746.1	c.31G>A	p.Val11Ile	missense_variant, NMD_transcript_variant	1/6

Frequencies

GnomAD3 genomes Cov.: 33

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

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000133

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000284

Gnomad4 OTH exome AF: 0.0000181

GnomAD4 genome Cov.: 33

Bravo AF: 0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Cardiovascular phenotype Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 13, 2021

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
MutationTaster	Benign	0.62	N
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
Varity_R		0.038
gMVP		0.11

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: rs1291588606; hg19: chr7-92077074;