7-92447892-AGCGGCGGCGGCG-AGCGGCGGCGGCGGCG

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP3BP6

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). Synonymous variant affecting the same amino acid position (i.e. F60F) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.00052 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000070 ( 0 hom. )

Consequence

GATAD1
NM_021167.5 conservative_inframe_insertion

Scores

Not classified

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:3

Conservation

PhyloP100: 0.310

Publications

1 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.

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 VariationId is 228693.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GATAD1	NM_021167.5 link	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
GATAD1	ENST00000287957.5 link	c.175_177dupGGC	p.Gly59dup	conservative_inframe_insertion	Exon 1 of 5	1	NM_021167.5	ENSP00000287957.3
GATAD1	ENST00000644160.1 link	n.31_33dupGGC		non_coding_transcript_exon_variant	Exon 1 of 2
GATAD1	ENST00000645746.1 link	n.175_177dupGGC		non_coding_transcript_exon_variant	Exon 1 of 6			ENSP00000493785.1
TMBIM7P	ENST00000641474.1 link	n.-82_-80dupCGC		upstream_gene_variant

Frequencies

GnomAD3 genomes

AF:

0.000514

AC:

AN:

151788

Hom.:

Cov.:

show subpopulations

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:

AN:

1114816

Hom.:

Cov.:

AF XY:

0.0000732

AC XY:

AN XY:

532730

show subpopulations

African (AFR)

AF:

0.00207

AC:

AN:

22720

American (AMR)

AF:

0.00

AC:

AN:

8228

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

14238

East Asian (EAS)

AF:

0.0000383

AC:

AN:

26106

South Asian (SAS)

AF:

0.0000398

AC:

AN:

25132

European-Finnish (FIN)

AF:

0.00

AC:

AN:

31686

Middle Eastern (MID)

AF:

0.000772

AC:

AN:

3888

European-Non Finnish (NFE)

AF:

0.0000192

AC:

AN:

938294

Other (OTH)

AF:

0.000180

AC:

AN:

44524

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.481

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000520

AC:

AN:

151896

Hom.:

Cov.:

AF XY:

0.000498

AC XY:

AN XY:

74272

show subpopulations

African (AFR)

AF:

0.00171

AC:

AN:

41464

American (AMR)

AF:

0.0000655

AC:

AN:

15258

Ashkenazi Jewish (ASJ)

AF:

0.000289

AC:

AN:

3464

East Asian (EAS)

AF:

0.00

AC:

AN:

5158

South Asian (SAS)

AF:

0.00

AC:

AN:

4820

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10526

Middle Eastern (MID)

AF:

0.00

AC:

AN:

290

European-Non Finnish (NFE)

AF:

0.0000736

AC:

AN:

67906

Other (OTH)

AF:

0.000475

AC:

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.479

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1Benign:3

Revision: criteria provided, conflicting classifications

LINK: link

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

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.31

Mutation Taster

=89/11

polymorphism

(source)

Splicing

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over