1-26057522-A-G

Position:

• chr1-26057522-A-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_032588.4(TRIM63):​c.854+106T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.193 in 1,435,878 control chromosomes in the GnomAD database, including 28,279 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.17 (2431 hom., cov: 31)
  • Exomes 𝑓: 0.20 (25848 hom.)
• Consequence: TRIM63 NM_032588.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -2.06

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

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BP6: Variant 1-26057522-A-G is Benign according to our data. Variant chr1-26057522-A-G is described in ClinVar as [Benign]. Clinvar id is 1287450.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.203 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TRIM63	NM_032588.4	c.854+106T>C		intron_variant		ENST00000374272.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TRIM63	ENST00000374272.4	c.854+106T>C		intron_variant		1	NM_032588.4	P1

Frequencies

GnomAD3 genomes AF: 0.172 AC: 26175 AN: 152032 Hom.: 2428 Cov.: 31

Gnomad AFR AF: 0.149

Gnomad AMI AF: 0.183

Gnomad AMR AF: 0.136

Gnomad ASJ AF: 0.181

Gnomad EAS AF: 0.0543

Gnomad SAS AF: 0.0969

Gnomad FIN AF: 0.187

Gnomad MID AF: 0.206

Gnomad NFE AF: 0.206

Gnomad OTH AF: 0.178

GnomAD4 exome AF: 0.195 AC: 250834 AN: 1283728 Hom.: 25848 Cov.: 19 AF XY: 0.193 AC XY: 122305 AN XY: 633594

Gnomad4 AFR exome AF: 0.146

Gnomad4 AMR exome AF: 0.0996

Gnomad4 ASJ exome AF: 0.181

Gnomad4 EAS exome AF: 0.0397

Gnomad4 SAS exome AF: 0.0997

Gnomad4 FIN exome AF: 0.188

Gnomad4 NFE exome AF: 0.213

Gnomad4 OTH exome AF: 0.184

GnomAD4 genome AF: 0.172 AC: 26205 AN: 152150 Hom.: 2431 Cov.: 31 AF XY: 0.168 AC XY: 12469 AN XY: 74386

Gnomad4 AFR AF: 0.149

Gnomad4 AMR AF: 0.136

Gnomad4 ASJ AF: 0.181

Gnomad4 EAS AF: 0.0543

Gnomad4 SAS AF: 0.0967

Gnomad4 FIN AF: 0.187

Gnomad4 NFE AF: 0.206

Gnomad4 OTH AF: 0.182

Alfa AF: 0.188 Hom.: 543

Bravo AF: 0.171

Asia WGS AF: 0.105 AC: 367 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Sep 04, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.026
DANN	Benign	0.45

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: rs12059101; hg19: chr1-26384013;