1-26057127-C-G

Position:

• chr1-26057127-C-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.979+76G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.017 in 1,570,394 control chromosomes in the GnomAD database, including 3,399 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.086 (1799 hom., cov: 31)
  • Exomes 𝑓: 0.0096 (1600 hom.)
• Consequence: TRIM63 NM_032588.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.00

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=-0.85).
• BP6: Variant 1-26057127-C-G is Benign according to our data. Variant chr1-26057127-C-G is described in ClinVar as [Benign]. Clinvar id is 1237163.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.289 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TRIM63	NM_032588.4	c.979+76G>C		intron_variant		ENST00000374272.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TRIM63	ENST00000374272.4	c.979+76G>C		intron_variant		1	NM_032588.4	P1

Frequencies

GnomAD3 genomes AF: 0.0859 AC: 12967 AN: 151008 Hom.: 1786 Cov.: 31

Gnomad AFR AF: 0.293

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0363

Gnomad ASJ AF: 0.000289

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00187

Gnomad FIN AF: 0.0000965

Gnomad MID AF: 0.0253

Gnomad NFE AF: 0.00260

Gnomad OTH AF: 0.0617

GnomAD4 exome AF: 0.00958 AC: 13599 AN: 1419268 Hom.: 1600 AF XY: 0.00849 AC XY: 5988 AN XY: 705694

Gnomad4 AFR exome AF: 0.299

Gnomad4 AMR exome AF: 0.0202

Gnomad4 ASJ exome AF: 0.000808

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00108

Gnomad4 FIN exome AF: 0.0000195

Gnomad4 NFE exome AF: 0.00140

Gnomad4 OTH exome AF: 0.0236

GnomAD4 genome AF: 0.0862 AC: 13022 AN: 151126 Hom.: 1799 Cov.: 31 AF XY: 0.0830 AC XY: 6126 AN XY: 73804

Gnomad4 AFR AF: 0.293

Gnomad4 AMR AF: 0.0362

Gnomad4 ASJ AF: 0.000289

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00208

Gnomad4 FIN AF: 0.0000965

Gnomad4 NFE AF: 0.00260

Gnomad4 OTH AF: 0.0611

Alfa AF: 0.00380 Hom.: 6

Bravo AF: 0.0977

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	May 21, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.19
DANN	Benign	0.69

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: rs1317428; hg19: chr1-26383618;