Genetic Variant NM_021167.5:c.57G>T (chr7-92447786-G-T) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_021167.5(GATAD1):c.57G>T(p.Met19Ile) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

GATAD1
NM_021167.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 5.16

Publications

0 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:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

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.57G>T	p.Met19Ile	missense	Exon 1 of 5	NP_066990.3
	GATAD1	NR_052016.2		n.305G>T		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.57G>T	p.Met19Ile	missense	Exon 1 of 5	ENSP00000287957.3	Q8WUU5
TMBIM7P	ENST00000641474.1		n.28C>A		non_coding_transcript_exon	Exon 1 of 10
GATAD1	ENST00000645746.1		n.57G>T		non_coding_transcript_exon	Exon 1 of 6	ENSP00000493785.1	A0A2R8Y4H1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1345632

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

663688

African (AFR)

AF:

0.00

AC:

AN:

26890

American (AMR)

AF:

0.00

AC:

AN:

28608

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

23506

East Asian (EAS)

AF:

0.00

AC:

AN:

28388

South Asian (SAS)

AF:

0.00

AC:

AN:

74926

European-Finnish (FIN)

AF:

0.00

AC:

AN:

47256

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5556

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1055128

Other (OTH)

AF:

0.00

AC:

AN:

55374

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.87

BayesDel_addAF

Pathogenic

0.20

BayesDel_noAF

Uncertain

0.050

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.020

Eigen

Benign

0.12

Eigen_PC

Benign

0.22

FATHMM_MKL

Uncertain

0.93

LIST_S2

Benign

0.84

M_CAP

Pathogenic

0.96

MetaRNN

Uncertain

0.49

MetaSVM

Pathogenic

1.1

MutationAssessor

Benign

1.1

PhyloP100

5.2

PrimateAI

Pathogenic

0.94

PROVEAN

Benign

-1.5

REVEL

Pathogenic

0.66

Sift

Benign

0.11

Sift4G

Benign

0.27

Polyphen

0.39

Vest4

0.48

MutPred

0.43

Loss of helix (P = 0.079)

MVP

0.61

MPC

0.46

ClinPred

0.93

GERP RS

4.5

PromoterAI

0.022

Neutral

(source)

Varity_R

0.68

gMVP

0.45

Mutation Taster

=62/38

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over