rs1789217100

Variant names:

• chr7-92447786-G-A
• rs1789217100
• NM_021167.5:c.57G>A

Your query was ambiguous. Multiple possible variants found:

• chr7-92447786-G-A
• chr7-92447786-G-T

Variant summary

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

The NM_021167.5(GATAD1):​c.57G>A​(p.Met19Ile) variant causes a missense change. The variant allele was found at a frequency of 0.000000743 in 1,345,632 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 7.4e-7 (0 hom.)
• Consequence: GATAD1 NM_021167.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.16
• 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: 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.57G>A	p.Met19Ile	missense	Exon 1 of 5	NP_066990.3
	GATAD1	NR_052016.2		n.305G>A		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.57G>A	p.Met19Ile	missense	Exon 1 of 5	ENSP00000287957.3	Q8WUU5
	TMBIM7P	ENST00000641474.1		n.28C>T		non_coding_transcript_exon	Exon 1 of 10
	GATAD1	ENST00000645746.1		n.57G>A		non_coding_transcript_exon	Exon 1 of 6	ENSP00000493785.1	A0A2R8Y4H1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 7.43e-7 AC: 1 AN: 1345632 Hom.: 0 Cov.: 31 AF XY: 0.00000151 AC XY: 1 AN XY: 663688

African (AFR) AF: 0.00 AC: 0 AN: 26890

American (AMR) AF: 0.00 AC: 0 AN: 28608

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23506

East Asian (EAS) AF: 0.00 AC: 0 AN: 28388

South Asian (SAS) AF: 0.00 AC: 0 AN: 74926

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 47256

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5556

European-Non Finnish (NFE) AF: 9.48e-7 AC: 1 AN: 1055128

Other (OTH) AF: 0.00 AC: 0 AN: 55374

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions as Germline

Significance: Uncertain significance

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.87
BayesDel_addAF	Pathogenic	0.20	D
BayesDel_noAF	Uncertain	0.050
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.020	T
Eigen	Benign	0.12
Eigen_PC	Benign	0.22
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Benign	0.84	T
M_CAP	Pathogenic	0.96	D
MetaRNN	Uncertain	0.49	T
MetaSVM	Pathogenic	1.1	D
MutationAssessor	Benign	1.1	L
PhyloP100		5.2
PrimateAI	Pathogenic	0.94	D
PROVEAN	Benign	-1.5	N
REVEL	Pathogenic	0.66
Sift	Benign	0.11	T
Sift4G	Benign	0.27	T
Polyphen		0.39	B
Vest4		0.48
MutPred		0.43		Loss of helix (P = 0.079)
MVP		0.61
MPC		0.46
ClinPred		0.93	D
GERP RS		4.5
PromoterAI		-0.031	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.68
gMVP		0.45
Mutation Taster		=62/38	polymorphism

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: rs1789217100; hg19: chr7-92077100;