Genetic Variant NM_021167.5:c.175_177dupGGC (chr7-92447892-A-AGCG) – ACMG Classification: Likely_benign (-2 pts)

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: Labcorp Genetics (formerly Invitae), Ambry Genetics

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.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GATAD1	NM_021167.5	MANE Select	c.175_177dupGGC	p.Gly59dup	conservative_inframe_insertion	Exon 1 of 5	NP_066990.3
	GATAD1	NR_052016.2		n.423_425dupGGC		non_coding_transcript_exon	Exon 1 of 6

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
GATAD1	ENST00000287957.5	TSL:1 MANE Select	c.175_177dupGGC	p.Gly59dup	conservative_inframe_insertion	Exon 1 of 5	ENSP00000287957.3	Q8WUU5
GATAD1	ENST00000644160.1		n.31_33dupGGC		non_coding_transcript_exon	Exon 1 of 2
GATAD1	ENST00000645746.1		n.175_177dupGGC		non_coding_transcript_exon	Exon 1 of 6	ENSP00000493785.1	A0A2R8Y4H1

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

ClinVar submissions

Significance:Conflicting classifications of pathogenicity

Revision:criteria provided, conflicting classifications

View on ClinVar

Pathogenic

VUS

Benign

Condition

Cardiovascular phenotype (1)

Dilated cardiomyopathy 2B (1)

GATAD1-related disorder (1)

not specified (1)

Computational scores

Source: dbNSFP v4.9

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over