chr1-26051871-C-T

Variant names:

• chr1-26051871-C-T
• rs77965623
• NM_032588.4:c.*2G>A

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_Strong BP6 BS2

The NM_032588.4(TRIM63):​c.*2G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00909 in 1,323,856 control chromosomes in the GnomAD database, including 68 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

• Frequency:
  • Genomes: 𝑓 0.0052 (4 hom., cov: 32)
  • Exomes 𝑓: 0.0096 (64 hom.)
• Consequence: TRIM63 NM_032588.4 3_prime_UTR
• Clinical Significance: Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1 B:5
• Conservation: PhyloP100: 0.400

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]

ACMG classification

Our verdict: Benign. The variant received -9 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BP6: Variant 1-26051871-C-T is Benign according to our data. Variant chr1-26051871-C-T is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 1285214.We mark this variant Likely_benign, oryginal submissions are: {Uncertain_significance=1, Likely_benign=2, Benign=1}. Variant chr1-26051871-C-T is described in Lovd as [Benign].
• BS2: High Homozygotes in GnomAd4 at 4 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRIM63	NM_032588.4	c.*2G>A		3_prime_UTR_variant	Exon 9 of 9	ENST00000374272.4	NP_115977.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TRIM63	ENST00000374272	c.*2G>A		3_prime_UTR_variant	Exon 9 of 9	1	NM_032588.4	ENSP00000363390.3

Frequencies

GnomAD3 genomes AF: 0.00520 AC: 790 AN: 151860 Hom.: 4 Cov.: 32

Gnomad AFR AF: 0.00198

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00301

Gnomad ASJ AF: 0.00115

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000832

Gnomad FIN AF: 0.00247

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00914

Gnomad OTH AF: 0.00335

GnomAD2 exomes AF: 0.00441 AC: 534 AN: 121188 AF XY: 0.00418

Gnomad AFR exome AF: 0.00168

Gnomad AMR exome AF: 0.00263

Gnomad ASJ exome AF: 0.00247

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00251

Gnomad NFE exome AF: 0.00664

Gnomad OTH exome AF: 0.00844

GnomAD4 exome AF: 0.00959 AC: 11241 AN: 1171876 Hom.: 64 Cov.: 32 AF XY: 0.00949 AC XY: 5364 AN XY: 565122

Gnomad4 AFR exome AF: 0.00133 AC: 33 AN: 24898

Gnomad4 AMR exome AF: 0.00327 AC: 57 AN: 17450

Gnomad4 ASJ exome AF: 0.00130 AC: 20 AN: 15372

Gnomad4 EAS exome AF: 0.00 AC: 0 AN: 30492

Gnomad4 SAS exome AF: 0.000499 AC: 15 AN: 30076

Gnomad4 FIN exome AF: 0.00307 AC: 126 AN: 41060

Gnomad4 NFE exome AF: 0.0111 AC: 10629 AN: 961392

Gnomad4 Remaining exome AF: 0.00771 AC: 360 AN: 46682

GnomAD4 genome AF: 0.00519 AC: 789 AN: 151980 Hom.: 4 Cov.: 32 AF XY: 0.00443 AC XY: 329 AN XY: 74300

Gnomad4 AFR AF: 0.00198 AC: 0.00197648 AN: 0.00197648

Gnomad4 AMR AF: 0.00301 AC: 0.00300929 AN: 0.00300929

Gnomad4 ASJ AF: 0.00115 AC: 0.00115473 AN: 0.00115473

Gnomad4 EAS AF: 0.00 AC: 0 AN: 0

Gnomad4 SAS AF: 0.000833 AC: 0.000833333 AN: 0.000833333

Gnomad4 FIN AF: 0.00247 AC: 0.00246586 AN: 0.00246586

Gnomad4 NFE AF: 0.00912 AC: 0.00912355 AN: 0.00912355

Gnomad4 OTH AF: 0.00331 AC: 0.00331126 AN: 0.00331126

Alfa AF: 0.00650 Hom.: 0

Bravo AF: 0.00526

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1 Benign:5

Revision: criteria provided, conflicting classifications

Submissions by phenotype

not specified Uncertain:1 Benign:3

-

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Apr 26, 2023

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

Genome Diagnostics Laboratory, University Medical Center Utrecht

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Apr 09, 2025

Molecular Diagnostic Laboratory for Inherited Cardiovascular Disease, Montreal Heart Institute

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jan 01, 2023

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

TRIM63: BS2 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	11
DANN	Benign	0.71
Mutation Taster		=99/1	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

Publications

LitVar

Other links and lift over

dbSNP: rs77965623; hg19: chr1-26378362;