rs201180188

Variant names:

• chr1-26053980-A-G
• rs201180188
• NM_032588.4:c.980-16T>C

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Strong BP6_Moderate

The NM_032588.4(TRIM63):​c.980-16T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000108 in 1,570,754 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.000033 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0000085 (0 hom.)
• Consequence: TRIM63 NM_032588.4 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.306
• Publications: 0 publications found

Genes affected

TRIM63 (HGNC:16007): (tripartite motif containing 63) This gene encodes a member of the RING zinc finger protein family found in striated muscle and iris. The product of this gene is an E3 ubiquitin ligase that localizes to the Z-line and M-line lattices of myofibrils. This protein plays an important role in the atrophy of skeletal and cardiac muscle and is required for the degradation of myosin heavy chain proteins, myosin light chain, myosin binding protein, and for muscle-type creatine kinase. [provided by RefSeq, Feb 2012]

TRIM63 Gene-Disease associations (from GenCC):

• hypertrophic cardiomyopathy

  Inheritance: AR, AD Classification: MODERATE, NO_KNOWN Submitted by: Ambry Genetics, ClinGen

ACMG classification

Our verdict: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 1-26053980-A-G is Benign according to our data. Variant chr1-26053980-A-G is described in ClinVar as Likely_benign. ClinVar VariationId is 2682350.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032588.4. 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
	TRIM63	NM_032588.4	MANE Select	c.980-16T>C		intron	N/A	NP_115977.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRIM63	ENST00000374272.4	TSL:1 MANE Select	c.980-16T>C		intron	N/A	ENSP00000363390.3	Q969Q1-1

Frequencies

GnomAD3 genomes AF: 0.0000329 AC: 5 AN: 152186 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000327

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000420 AC: 9 AN: 214252 AF XY: 0.0000170

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000346

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.000202

GnomAD4 exome AF: 0.00000846 AC: 12 AN: 1418450 Hom.: 0 Cov.: 27 AF XY: 0.00000708 AC XY: 5 AN XY: 706076

African (AFR) AF: 0.00 AC: 0 AN: 30428

American (AMR) AF: 0.000295 AC: 10 AN: 33878

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24802

East Asian (EAS) AF: 0.00 AC: 0 AN: 37506

South Asian (SAS) AF: 0.00 AC: 0 AN: 80370

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52586

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5636

European-Non Finnish (NFE) AF: 0.00000183 AC: 2 AN: 1094652

Other (OTH) AF: 0.00 AC: 0 AN: 58592

GnomAD4 genome AF: 0.0000328 AC: 5 AN: 152304 Hom.: 0 Cov.: 33 AF XY: 0.0000269 AC XY: 2 AN XY: 74468

African (AFR) AF: 0.00 AC: 0 AN: 41572

American (AMR) AF: 0.000327 AC: 5 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5190

South Asian (SAS) AF: 0.00 AC: 0 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10610

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68022

Other (OTH) AF: 0.00 AC: 0 AN: 2108

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000189

ClinVar

ClinVar submissions as Germline

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	4.2
DANN	Benign	0.66
PhyloP100		-0.31

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: rs201180188; hg19: chr1-26380471;