rs61749354

Variant names:

• chr1-26053903-C-T
• rs61749354
• NM_032588.4:c.1041G>A

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BA1

The NM_032588.4(TRIM63):​c.1041G>A​(p.Gly347Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0031 in 1,593,200 control chromosomes in the GnomAD database, including 167 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0057 (28 hom., cov: 33)
  • Exomes 𝑓: 0.0028 (139 hom.)
• Consequence: TRIM63 NM_032588.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -0.589
• Publications: 4 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: Benign. The variant received -19 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.44).
• BP6: Variant 1-26053903-C-T is Benign according to our data. Variant chr1-26053903-C-T is described in ClinVar as Benign. ClinVar VariationId is 1283076.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.589 with no splicing effect.
• BA1: GnomAdExome4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0713 is higher than 0.05.

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.1041G>A	p.Gly347Gly	synonymous	Exon 8 of 9	NP_115977.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRIM63	ENST00000374272.4	TSL:1 MANE Select	c.1041G>A	p.Gly347Gly	synonymous	Exon 8 of 9	ENSP00000363390.3	Q969Q1-1

Frequencies

GnomAD3 genomes AF: 0.00570 AC: 868 AN: 152166 Hom.: 26 Cov.: 33

Gnomad AFR AF: 0.00159

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0435

Gnomad ASJ AF: 0.000864

Gnomad EAS AF: 0.0140

Gnomad SAS AF: 0.000415

Gnomad FIN AF: 0.00226

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000309

Gnomad OTH AF: 0.00670

GnomAD2 exomes AF: 0.0105 AC: 2428 AN: 230158 AF XY: 0.00805

Gnomad AFR exome AF: 0.00180

Gnomad AMR exome AF: 0.0765

Gnomad ASJ exome AF: 0.00153

Gnomad EAS exome AF: 0.0120

Gnomad FIN exome AF: 0.00212

Gnomad NFE exome AF: 0.000296

Gnomad OTH exome AF: 0.00851

GnomAD4 exome AF: 0.00282 AC: 4059 AN: 1440916 Hom.: 139 Cov.: 29 AF XY: 0.00254 AC XY: 1822 AN XY: 717250

African (AFR) AF: 0.000812 AC: 26 AN: 32032

American (AMR) AF: 0.0736 AC: 2786 AN: 37842

Ashkenazi Jewish (ASJ) AF: 0.00138 AC: 35 AN: 25390

East Asian (EAS) AF: 0.0182 AC: 709 AN: 39034

South Asian (SAS) AF: 0.000518 AC: 43 AN: 83068

European-Finnish (FIN) AF: 0.00196 AC: 104 AN: 53174

Middle Eastern (MID) AF: 0.000350 AC: 2 AN: 5722

European-Non Finnish (NFE) AF: 0.000176 AC: 194 AN: 1105106

Other (OTH) AF: 0.00269 AC: 160 AN: 59548

GnomAD4 genome AF: 0.00573 AC: 873 AN: 152284 Hom.: 28 Cov.: 33 AF XY: 0.00623 AC XY: 464 AN XY: 74470

African (AFR) AF: 0.00159 AC: 66 AN: 41560

American (AMR) AF: 0.0439 AC: 671 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.000864 AC: 3 AN: 3472

East Asian (EAS) AF: 0.0141 AC: 73 AN: 5186

South Asian (SAS) AF: 0.000415 AC: 2 AN: 4820

European-Finnish (FIN) AF: 0.00226 AC: 24 AN: 10616

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

European-Non Finnish (NFE) AF: 0.000309 AC: 21 AN: 68014

Other (OTH) AF: 0.00616 AC: 13 AN: 2112

Alfa AF: 0.00447 Hom.: 23

Bravo AF: 0.00966

Asia WGS AF: 0.00751 AC: 26 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	2	not specified (2)
-	-	1	TRIM63-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.44
CADD	Benign	6.2
DANN	Benign	0.58
PhyloP100		-0.59
Mutation Taster		=99/1	polymorphism (auto)

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: rs61749354; hg19: chr1-26380394; COSMIC: COSV100958133; COSMIC: COSV100958133;