7-92447892-AGCGGCGGCGGCG-AGCGGCGGCG

Variant names:

• chr7-92447892-AGCG-A
• rs876657812
• NM_021167.5:c.175_177delGGC

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BP3

The NM_021167.5(GATAD1):​c.175_177delGGC​(p.Gly59del) variant causes a conservative inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000431 in 1,114,314 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.000043 (0 hom.)
• Consequence: GATAD1 NM_021167.5 conservative_inframe_deletion
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.08
• Publications: 1 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: Likely_benign. The variant received -1 ACMG points.

• BP3: Nonframeshift variant in repetitive region in NM_021167.5

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_021167.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GATAD1	NM_021167.5	MANE Select	c.175_177delGGC	p.Gly59del	conservative_inframe_deletion	Exon 1 of 5	NP_066990.3
	GATAD1	NR_052016.2		n.423_425delGGC		non_coding_transcript_exon	Exon 1 of 6

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GATAD1	ENST00000287957.5	TSL:1 MANE Select	c.175_177delGGC	p.Gly59del	conservative_inframe_deletion	Exon 1 of 5	ENSP00000287957.3
	GATAD1	ENST00000644160.1		n.31_33delGGC		non_coding_transcript_exon	Exon 1 of 2
	GATAD1	ENST00000645746.1		n.175_177delGGC		non_coding_transcript_exon	Exon 1 of 6	ENSP00000493785.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.000165 AC: 1 AN: 6072 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: 0.000185

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000431 AC: 48 AN: 1114314 Hom.: 0 AF XY: 0.0000563 AC XY: 30 AN XY: 532462

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.0000440 AC: 1 AN: 22712

American (AMR) AF: 0.00 AC: 0 AN: 8222

Ashkenazi Jewish (ASJ) AF: 0.000141 AC: 2 AN: 14230

East Asian (EAS) AF: 0.0000383 AC: 1 AN: 26094

South Asian (SAS) AF: 0.000239 AC: 6 AN: 25096

European-Finnish (FIN) AF: 0.000126 AC: 4 AN: 31664

Middle Eastern (MID) AF: 0.000257 AC: 1 AN: 3888

European-Non Finnish (NFE) AF: 0.0000331 AC: 31 AN: 937902

Other (OTH) AF: 0.0000449 AC: 2 AN: 44506

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.1
Mutation Taster		=89/11	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: rs876657812; hg19: chr7-92077206;