7-92447892-AGCGGCGGCGGCG-AGCGGCGGCGGCGGCG

Variant names:

• chr7-92447892-A-AGCG
• rs876657812
• NM_021167.5:c.175_177dupGGC

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP3 BP6

The NM_021167.5(GATAD1):​c.175_177dupGGC​(p.Gly59dup) variant causes a conservative inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000124 in 1,266,712 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

• Frequency:
  • Genomes: 𝑓 0.00052 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000070 (0 hom.)
• Consequence: GATAD1 NM_021167.5 conservative_inframe_insertion
• Clinical Significance: Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1 B:3
• Conservation: PhyloP100: 0.310

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
• BP3: Nonframeshift variant in repetitive region in NM_021167.5
• BP6: Variant 7-92447892-A-AGCG is Benign according to our data. Variant chr7-92447892-A-AGCG is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 228693.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=2, Uncertain_significance=1}.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GATAD1	NM_021167.5	c.175_177dupGGC	p.Gly59dup	conservative_inframe_insertion	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.175_177dupGGC	p.Gly59dup	conservative_inframe_insertion	Exon 1 of 5	1	NM_021167.5	ENSP00000287957.3
GATAD1	ENST00000644160.1	n.31_33dupGGC		non_coding_transcript_exon_variant	Exon 1 of 2
GATAD1	ENST00000645746.1	n.175_177dupGGC		non_coding_transcript_exon_variant	Exon 1 of 6			ENSP00000493785.1
TMBIM7P	ENST00000641474.1	n.-82_-80dupCGC		upstream_gene_variant

Frequencies

GnomAD3 genomes AF: 0.000514 AC: 78 AN: 151788 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00169

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000656

Gnomad ASJ AF: 0.000289

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000736

Gnomad OTH AF: 0.000480

GnomAD4 exome AF: 0.0000700 AC: 78 AN: 1114816 Hom.: 0 Cov.: 31 AF XY: 0.0000732 AC XY: 39 AN XY: 532730

Gnomad4 AFR exome AF: 0.00207

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000383

Gnomad4 SAS exome AF: 0.0000398

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000192

Gnomad4 OTH exome AF: 0.000180

GnomAD4 genome AF: 0.000520 AC: 79 AN: 151896 Hom.: 0 Cov.: 33 AF XY: 0.000498 AC XY: 37 AN XY: 74272

Gnomad4 AFR AF: 0.00171

Gnomad4 AMR AF: 0.0000655

Gnomad4 ASJ AF: 0.000289

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000736

Gnomad4 OTH AF: 0.000475

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1 Benign:3

Revision: criteria provided, conflicting classifications

Submissions by phenotype

not specified Uncertain:1

Sep 22, 2015

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The p.Gly59dup variant in GATAD1 has not been previously reported in individuals with DCM and data from large population studies is insufficient to assess the f requency of this variant. This variant results in the duplication of a glycine r esidue at position 59 and is not predicted to alter the protein reading-frame. I n summary, the clinical significance of the p.Gly59dup variant is uncertain. -

GATAD1-related disorder Benign:1

Feb 24, 2022

PreventionGenetics, part of Exact Sciences

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Dilated cardiomyopathy 2B Benign:1

Jan 30, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Cardiovascular phenotype Benign:1

Feb 10, 2023

Ambry Genetics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs876657812; hg19: chr7-92077206;