NM_032588.4:c.855-57T>C

Variant names:

• chr1-26057384-A-G
• rs2275947
• NM_032588.4:c.855-57T>C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_032588.4(TRIM63):​c.855-57T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.216 in 1,594,192 control chromosomes in the GnomAD database, including 41,246 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.28 (7280 hom., cov: 32)
  • Exomes 𝑓: 0.21 (33966 hom.)
• Consequence: TRIM63 NM_032588.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.859
• Publications: 8 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: ClinGen, Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 1-26057384-A-G is Benign according to our data. Variant chr1-26057384-A-G is described in ClinVar as Benign. ClinVar VariationId is 1267089.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.486 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.855-57T>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.855-57T>C		intron	N/A	ENSP00000363390.3	Q969Q1-1

Frequencies

GnomAD3 genomes AF: 0.278 AC: 42184 AN: 151996 Hom.: 7249 Cov.: 32

Gnomad AFR AF: 0.491

Gnomad AMI AF: 0.184

Gnomad AMR AF: 0.185

Gnomad ASJ AF: 0.186

Gnomad EAS AF: 0.176

Gnomad SAS AF: 0.104

Gnomad FIN AF: 0.187

Gnomad MID AF: 0.241

Gnomad NFE AF: 0.209

Gnomad OTH AF: 0.258

GnomAD4 exome AF: 0.209 AC: 301486 AN: 1442078 Hom.: 33966 Cov.: 31 AF XY: 0.206 AC XY: 147196 AN XY: 716094

African (AFR) AF: 0.499 AC: 16353 AN: 32754

American (AMR) AF: 0.119 AC: 4989 AN: 41996

Ashkenazi Jewish (ASJ) AF: 0.188 AC: 4679 AN: 24906

East Asian (EAS) AF: 0.160 AC: 6336 AN: 39488

South Asian (SAS) AF: 0.105 AC: 8806 AN: 83640

European-Finnish (FIN) AF: 0.188 AC: 9866 AN: 52512

Middle Eastern (MID) AF: 0.237 AC: 1075 AN: 4544

European-Non Finnish (NFE) AF: 0.214 AC: 236492 AN: 1102920

Other (OTH) AF: 0.217 AC: 12890 AN: 59318

GnomAD4 genome AF: 0.278 AC: 42265 AN: 152114 Hom.: 7280 Cov.: 32 AF XY: 0.271 AC XY: 20131 AN XY: 74370

African (AFR) AF: 0.492 AC: 20392 AN: 41452

American (AMR) AF: 0.185 AC: 2830 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.186 AC: 644 AN: 3470

East Asian (EAS) AF: 0.176 AC: 908 AN: 5168

South Asian (SAS) AF: 0.104 AC: 502 AN: 4824

European-Finnish (FIN) AF: 0.187 AC: 1982 AN: 10592

Middle Eastern (MID) AF: 0.241 AC: 71 AN: 294

European-Non Finnish (NFE) AF: 0.209 AC: 14219 AN: 67986

Other (OTH) AF: 0.260 AC: 550 AN: 2114

Alfa AF: 0.237 Hom.: 13343

Bravo AF: 0.292

Asia WGS AF: 0.159 AC: 559 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	6.3
DANN	Benign	0.62
PhyloP100		0.86
Mutation Taster		=100/0	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: rs2275947; hg19: chr1-26383875; COSMIC: COSV65328024; COSMIC: COSV65328024;