chr1-26057384-A-G

Position:

• chr1-26057384-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.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

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=-0.88).
• BP6: Variant 1-26057384-A-G is Benign according to our data. Variant chr1-26057384-A-G is described in ClinVar as [Benign]. Clinvar id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TRIM63	NM_032588.4	c.855-57T>C		intron_variant		ENST00000374272.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TRIM63	ENST00000374272.4	c.855-57T>C		intron_variant		1	NM_032588.4	P1

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

Gnomad4 AFR exome AF: 0.499

Gnomad4 AMR exome AF: 0.119

Gnomad4 ASJ exome AF: 0.188

Gnomad4 EAS exome AF: 0.160

Gnomad4 SAS exome AF: 0.105

Gnomad4 FIN exome AF: 0.188

Gnomad4 NFE exome AF: 0.214

Gnomad4 OTH exome AF: 0.217

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

Gnomad4 AFR AF: 0.492

Gnomad4 AMR AF: 0.185

Gnomad4 ASJ AF: 0.186

Gnomad4 EAS AF: 0.176

Gnomad4 SAS AF: 0.104

Gnomad4 FIN AF: 0.187

Gnomad4 NFE AF: 0.209

Gnomad4 OTH AF: 0.260

Alfa AF: 0.221 Hom.: 6611

Bravo AF: 0.292

Asia WGS AF: 0.159 AC: 559 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	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Sep 04, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	6.3
DANN	Benign	0.62

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: rs2275947; hg19: chr1-26383875; COSMIC: COSV65328024; COSMIC: COSV65328024;