7-92447734-C-T

Variant names:

• chr7-92447734-C-T
• rs986259274
• NM_021167.5:c.5C>T

Variant summary

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

The NM_021167.5(GATAD1):​c.5C>T​(p.Pro2Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00000376 in 1,328,408 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P2S) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000038 (0 hom.)
• Consequence: GATAD1 NM_021167.5 missense
• Clinical Significance: Uncertain significance criteria provided, multiple submitters, no conflicts U:2
• Conservation: PhyloP100: 3.86
• Publications: 1 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: Labcorp Genetics (formerly Invitae), Ambry Genetics

TMBIM7P (HGNC:):

ACMG classification

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.5C>T	p.Pro2Leu	missense	Exon 1 of 5	NP_066990.3
	GATAD1	NR_052016.2		n.253C>T		non_coding_transcript_exon	Exon 1 of 6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GATAD1	ENST00000287957.5	TSL:1 MANE Select	c.5C>T	p.Pro2Leu	missense	Exon 1 of 5	ENSP00000287957.3	Q8WUU5
	GATAD1	ENST00000645746.1		n.5C>T		non_coding_transcript_exon	Exon 1 of 6	ENSP00000493785.1	A0A2R8Y4H1
	TMBIM7P	ENST00000641474.1		n.61+19G>A		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000376 AC: 5 AN: 1328408 Hom.: 0 Cov.: 31 AF XY: 0.00000305 AC XY: 2 AN XY: 655212

African (AFR) AF: 0.00 AC: 0 AN: 26130

American (AMR) AF: 0.00 AC: 0 AN: 24934

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22768

East Asian (EAS) AF: 0.0000356 AC: 1 AN: 28074

South Asian (SAS) AF: 0.00 AC: 0 AN: 73086

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 46712

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5474

European-Non Finnish (NFE) AF: 0.00000382 AC: 4 AN: 1046816

Other (OTH) AF: 0.00 AC: 0 AN: 54414

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions as Germline

Significance: Uncertain significance

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	1	-	Cardiovascular phenotype (1)
-	1	-	Dilated cardiomyopathy 2B (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.97
BayesDel_addAF	Uncertain	0.12	D
BayesDel_noAF	Uncertain	-0.060
CADD	Pathogenic	30
DANN	Uncertain	1.0
DEOGEN2	Benign	0.11	T
Eigen	Benign	-0.071
Eigen_PC	Benign	0.020
FATHMM_MKL	Benign	0.60	D
LIST_S2	Uncertain	0.89	D
M_CAP	Pathogenic	0.99	D
MetaRNN	Uncertain	0.49	T
MetaSVM	Benign	-0.56	T
MutationAssessor	Uncertain	2.5	M
PhyloP100		3.9
PrimateAI	Pathogenic	0.86	D
PROVEAN	Pathogenic	-6.1	D
REVEL	Uncertain	0.40
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		0.014	B
Vest4		0.49
MutPred		0.47		Gain of stability (P = 0.0061)
MVP		0.39
MPC		1.0
ClinPred		0.99	D
GERP RS		3.5
PromoterAI		0.050	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.82
gMVP		0.52
Mutation Taster		=59/41	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs986259274; hg19: chr7-92077048;