rs387907188

Variant names:

• chr7-92448806-T-C
• rs387907188
• NM_021167.5:c.304T>C

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP5

The NM_021167.5(GATAD1):​c.304T>C​(p.Ser102Pro) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (no stars). Synonymous variant affecting the same amino acid position (i.e. S102S) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: GATAD1 NM_021167.5 missense
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 5.29
• Publications: 7 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)

ACMG classification

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 7-92448806-T-C is Pathogenic according to our data. Variant chr7-92448806-T-C is described in ClinVar as Pathogenic. ClinVar VariationId is 31656.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GATAD1	NM_021167.5	c.304T>C	p.Ser102Pro	missense_variant	Exon 2 of 5	ENST00000287957.5	NP_066990.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GATAD1	ENST00000287957.5	c.304T>C	p.Ser102Pro	missense_variant	Exon 2 of 5	1	NM_021167.5	ENSP00000287957.3
GATAD1	ENST00000644160.1	n.160T>C		non_coding_transcript_exon_variant	Exon 2 of 2
GATAD1	ENST00000645746.1	n.304T>C		non_coding_transcript_exon_variant	Exon 2 of 6			ENSP00000493785.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 28

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Dilated cardiomyopathy 2B Pathogenic:1

Dec 01, 2011

OMIM

Significance: Pathogenic

Review Status: no assertion criteria provided

Collection Method: literature only

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.38
BayesDel_addAF	Pathogenic	0.26	D
BayesDel_noAF	Uncertain	0.13
CADD	Uncertain	23
DANN	Benign	0.97
DEOGEN2	Benign	0.013	T
Eigen	Uncertain	0.54
Eigen_PC	Uncertain	0.56
FATHMM_MKL	Uncertain	0.86	D
LIST_S2	Benign	0.71	T
M_CAP	Benign	0.067	D
MetaRNN	Uncertain	0.69	D
MetaSVM	Benign	-0.58	T
MutationAssessor	Benign	0.49	N
PhyloP100		5.3
PrimateAI	Pathogenic	0.84	D
PROVEAN	Benign	-1.9	N
REVEL	Uncertain	0.34
Sift	Benign	0.22	T
Sift4G	Benign	0.27	T
Polyphen		0.99	D
Vest4		0.81
MutPred		0.21		Loss of phosphorylation at S102 (P = 0.0335);
MVP		0.73
MPC		0.49
ClinPred		0.82	D
GERP RS		5.4
Varity_R		0.48
gMVP		0.48
Mutation Taster		=30/70	disease causing (ClinVar)

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: rs387907188; hg19: chr7-92078120;