NM_021167.5:c.-217C>T

Variant names:

• chr7-92447513-C-T
• rs146395954
• NM_021167.5:c.-217C>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_021167.5(GATAD1):​c.-217C>T variant causes a 5 prime UTR 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.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: GATAD1 NM_021167.5 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.833
• 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)

TMBIM7P (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.75).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GATAD1	NM_021167.5	c.-217C>T		5_prime_UTR_variant	Exon 1 of 5	ENST00000287957.5	NP_066990.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GATAD1	ENST00000287957.5	c.-217C>T		5_prime_UTR_variant	Exon 1 of 5	1	NM_021167.5	ENSP00000287957.3
GATAD1	ENST00000645746.1	n.-217C>T		non_coding_transcript_exon_variant	Exon 1 of 6			ENSP00000493785.1
GATAD1	ENST00000645746.1	n.-217C>T		5_prime_UTR_variant	Exon 1 of 6			ENSP00000493785.1
TMBIM7P	ENST00000641474.1	n.61+240G>A		intron_variant	Intron 1 of 9

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 271734 Hom.: 0 Cov.: 5 AF XY: 0.00 AC XY: 0 AN XY: 140306

African (AFR) AF: 0.00 AC: 0 AN: 6132

American (AMR) AF: 0.00 AC: 0 AN: 4744

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 7340

East Asian (EAS) AF: 0.00 AC: 0 AN: 15450

South Asian (SAS) AF: 0.00 AC: 0 AN: 16662

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 16880

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1158

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 188976

Other (OTH) AF: 0.00 AC: 0 AN: 14392

GnomAD4 genome Cov.: 33

Alfa AF: 0.0000541 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	5.4
DANN	Benign	0.94
PhyloP100		-0.83
PromoterAI		0.0046	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs146395954; hg19: chr7-92076827;