chr7-92456449-C-G

Variant names:

• chr7-92456449-C-G
• rs34768413
• NM_021167.5:c.697C>G

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_021167.5(GATAD1):​c.697C>G​(p.Arg233Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. 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: not found (cov: 32)
• Consequence: GATAD1 NM_021167.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.27
• Publications: 0 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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.26623344).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GATAD1	NM_021167.5	c.697C>G	p.Arg233Gly	missense_variant	Exon 5 of 5	ENST00000287957.5	NP_066990.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GATAD1	ENST00000287957.5	c.697C>G	p.Arg233Gly	missense_variant	Exon 5 of 5	1	NM_021167.5	ENSP00000287957.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.37
BayesDel_addAF	Pathogenic	0.17	D
BayesDel_noAF	Uncertain	0.010
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.13	T
Eigen	Benign	0.072
Eigen_PC	Benign	0.095
FATHMM_MKL	Uncertain	0.83	D
LIST_S2	Uncertain	0.93	D
M_CAP	Benign	0.040	D
MetaRNN	Benign	0.27	T
MetaSVM	Benign	-0.83	T
MutationAssessor	Uncertain	2.2	M
PhyloP100		1.3
PrimateAI	Uncertain	0.73	T
PROVEAN	Pathogenic	-5.4	D
REVEL	Benign	0.28
Sift	Uncertain	0.013	D
Sift4G	Uncertain	0.0040	D
Polyphen		0.65	P
Vest4		0.50
MutPred		0.18		Gain of relative solvent accessibility (P = 0.0166);
MVP		0.59
MPC		0.59
ClinPred		0.94	D
GERP RS		3.5
Varity_R		0.42
gMVP		0.62
Mutation Taster		=46/54	disease causing

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: rs34768413; hg19: chr7-92085763;