Variant 1-26053903-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_032588.4(TRIM63):c.1041G>A(p.Gly347=) 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

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.589

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TRIM63	NM_032588.4 linkuse as main transcript	c.1041G>A	p.Gly347=	synonymous_variant	8/9	ENST00000374272.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TRIM63	ENST00000374272.4 linkuse as main transcript	c.1041G>A	p.Gly347=	synonymous_variant	8/9	1	NM_032588.4	P1	Q969Q1-1

Frequencies

GnomAD3 genomes

AF:

0.00570

AC:

868

AN:

152166

Hom.:

Cov.:

show subpopulations

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

GnomAD3 exomes

AF:

0.0105

AC:

2428

AN:

230158

Hom.:

100

AF XY:

0.00805

AC XY:

1009

AN XY:

125372

show subpopulations

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 SAS exome

AF:

0.000405

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.:

AF XY:

0.00254

AC XY:

1822

AN XY:

717250

show subpopulations

Gnomad4 AFR exome

AF:

0.000812

Gnomad4 AMR exome

AF:

0.0736

Gnomad4 ASJ exome

AF:

0.00138

Gnomad4 EAS exome

AF:

0.0182

Gnomad4 SAS exome

AF:

0.000518

Gnomad4 FIN exome

AF:

0.00196

Gnomad4 NFE exome

AF:

0.000176

Gnomad4 OTH exome

AF:

0.00269

GnomAD4 genome

AF:

0.00573

AC:

873

AN:

152284

Hom.:

Cov.:

AF XY:

0.00623

AC XY:

464

AN XY:

74470

show subpopulations

Gnomad4 AFR

AF:

0.00159

Gnomad4 AMR

AF:

0.0439

Gnomad4 ASJ

AF:

0.000864

Gnomad4 EAS

AF:

0.0141

Gnomad4 SAS

AF:

0.000415

Gnomad4 FIN

AF:

0.00226

Gnomad4 NFE

AF:

0.000309

Gnomad4 OTH

AF:

0.00616

Alfa

AF:

0.00161

Hom.:

Bravo

AF:

0.00966

Asia WGS

AF:

0.00751

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

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

Apr 17, 2023

- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 05, 2021

- -

TRIM63-related disorder

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Aug 07, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.44

CADD

Benign

6.2

DANN

Benign

0.58

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over