7-92456449-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_021167.5(GATAD1):c.697C>T(p.Arg233Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0147 in 1,611,378 control chromosomes in the GnomAD database, including 234 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R233Q) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.010 ( 16 hom., cov: 32)

Exomes 𝑓: 0.015 ( 218 hom. )

Consequence

GATAD1
NM_021167.5 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: 1.27

Publications

17 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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.008320868).

BP6

Variant 7-92456449-C-T is Benign according to our data. Variant chr7-92456449-C-T is described in ClinVar as Benign. ClinVar VariationId is 45829.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population mid. GnomAdExome4 allele frequency = 0.0152 (22210/1459056) while in subpopulation MID AF = 0.0193 (111/5766). AF 95% confidence interval is 0.0176. There are 218 homozygotes in GnomAdExome4. There are 11048 alleles in the male GnomAdExome4 subpopulation. Median coverage is 29. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 16 AR,AD gene

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.697C>T	p.Arg233Trp	missense	Exon 5 of 5	NP_066990.3
	GATAD1	NR_052016.2		n.945C>T		non_coding_transcript_exon	Exon 5 of 6

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
GATAD1	ENST00000287957.5	TSL:1 MANE Select	c.697C>T	p.Arg233Trp	missense	Exon 5 of 5	ENSP00000287957.3	Q8WUU5
GATAD1	ENST00000493878.1	TSL:1	n.1305C>T		non_coding_transcript_exon	Exon 3 of 3
GATAD1	ENST00000465247.1	TSL:2	n.709C>T		non_coding_transcript_exon	Exon 2 of 2

Frequencies

GnomAD3 genomes

AF:

0.0100

AC:

1525

AN:

152204

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00241

Gnomad AMI

AF:

0.0395

Gnomad AMR

AF:

0.0101

Gnomad ASJ

AF:

0.00374

Gnomad EAS

AF:

0.000385

Gnomad SAS

AF:

0.00207

Gnomad FIN

AF:

0.0135

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.0152

Gnomad OTH

AF:

0.0120

GnomAD2 exomes

AF:

0.0109

AC:

2734

AN:

251366

AF XY:

0.0114

show subpopulations

Gnomad AFR exome

AF:

0.00215

Gnomad AMR exome

AF:

0.00654

Gnomad ASJ exome

AF:

0.00437

Gnomad EAS exome

AF:

0.000381

Gnomad FIN exome

AF:

0.0133

Gnomad NFE exome

AF:

0.0170

Gnomad OTH exome

AF:

0.0148

GnomAD4 exome

AF:

0.0152

AC:

22210

AN:

1459056

Hom.:

218

Cov.:

AF XY:

0.0152

AC XY:

11048

AN XY:

725958

show subpopulations

African (AFR)

AF:

0.00287

AC:

AN:

33426

American (AMR)

AF:

0.00725

AC:

324

AN:

44698

Ashkenazi Jewish (ASJ)

AF:

0.00525

AC:

137

AN:

26108

East Asian (EAS)

AF:

0.000403

AC:

AN:

39692

South Asian (SAS)

AF:

0.00339

AC:

292

AN:

86198

European-Finnish (FIN)

AF:

0.0140

AC:

750

AN:

53410

Middle Eastern (MID)

AF:

0.0193

AC:

111

AN:

5766

European-Non Finnish (NFE)

AF:

0.0178

AC:

19705

AN:

1109472

Other (OTH)

AF:

0.0129

AC:

779

AN:

60286

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.463

Heterozygous variant carriers

960

1920

2879

3839

4799

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

738

1476

2214

2952

3690

<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:

0.0100

AC:

1525

AN:

152322

Hom.:

Cov.:

AF XY:

0.00975

AC XY:

726

AN XY:

74484

show subpopulations

African (AFR)

AF:

0.00240

AC:

100

AN:

41584

American (AMR)

AF:

0.0101

AC:

155

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.00374

AC:

AN:

3472

East Asian (EAS)

AF:

0.000386

AC:

AN:

5182

South Asian (SAS)

AF:

0.00207

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.0135

AC:

143

AN:

10618

Middle Eastern (MID)

AF:

0.0170

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0152

AC:

1036

AN:

68020

Other (OTH)

AF:

0.0118

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

154

232

309

386

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<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:

0.0147

Hom.:

Bravo

AF:

0.00982

TwinsUK

AF:

0.0181

AC:

ALSPAC

AF:

0.0231

AC:

ESP6500AA

AF:

0.00182

AC:

ESP6500EA

AF:

0.0155

AC:

133

ExAC

AF:

0.0111

AC:

1353

Asia WGS

AF:

0.00318

AC:

AN:

3478

EpiCase

AF:

0.0161

EpiControl

AF:

0.0162

ClinVar

ClinVar submissions as Germline

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (4)

Dilated cardiomyopathy 2B (2)

Hypertrophic cardiomyopathy 2 (1)

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.22

BayesDel_addAF

Benign

-0.33

BayesDel_noAF

Benign

-0.23

CADD

Pathogenic

(source)

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.20

Eigen

Uncertain

0.29

Eigen_PC

Uncertain

0.25

FATHMM_MKL

Uncertain

0.79

LIST_S2

Uncertain

0.97

MetaRNN

Benign

0.0083

MetaSVM

Benign

-0.81

MutationAssessor

Uncertain

2.2

PhyloP100

1.3

PrimateAI

Pathogenic

0.81

PROVEAN

Pathogenic

-6.6

REVEL

Benign

0.22

Sift

Uncertain

0.0020

Sift4G

Pathogenic

0.0010

Polyphen

1.0

Vest4

0.061

MPC

0.79

ClinPred

0.057

GERP RS

3.5

Varity_R

0.47

gMVP

0.68

Mutation Taster

=83/17

polymorphism

(source)

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

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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