chr1-26057154-CCAGGGGT-C

Position:

• chr1-26057154-CCAGGGGT-C

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_032588.4(TRIM63):​c.979+42_979+48del variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.222 in 1,606,778 control chromosomes in the GnomAD database, including 44,214 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.17 (2926 hom., cov: 27)
  • Exomes 𝑓: 0.23 (41288 hom.)
• Consequence: TRIM63 NM_032588.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.16

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 -10 ACMG points.

• BP6: Variant 1-26057154-CCAGGGGT-C is Benign according to our data. Variant chr1-26057154-CCAGGGGT-C is described in ClinVar as [Benign]. Clinvar id is 1275187.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.251 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TRIM63	NM_032588.4	c.979+42_979+48del		intron_variant		ENST00000374272.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TRIM63	ENST00000374272.4	c.979+42_979+48del		intron_variant		1	NM_032588.4	P1

Frequencies

GnomAD3 genomes AF: 0.170 AC: 25798 AN: 151904 Hom.: 2928 Cov.: 27

Gnomad AFR AF: 0.0420

Gnomad AMI AF: 0.259

Gnomad AMR AF: 0.140

Gnomad ASJ AF: 0.189

Gnomad EAS AF: 0.00212

Gnomad SAS AF: 0.108

Gnomad FIN AF: 0.265

Gnomad MID AF: 0.196

Gnomad NFE AF: 0.255

Gnomad OTH AF: 0.173

GnomAD3 exomes AF: 0.181 AC: 44901 AN: 247648 Hom.: 4862 AF XY: 0.185 AC XY: 24821 AN XY: 133846

Gnomad AFR exome AF: 0.0401

Gnomad AMR exome AF: 0.110

Gnomad ASJ exome AF: 0.194

Gnomad EAS exome AF: 0.000927

Gnomad SAS exome AF: 0.126

Gnomad FIN exome AF: 0.265

Gnomad NFE exome AF: 0.250

Gnomad OTH exome AF: 0.204

GnomAD4 exome AF: 0.228 AC: 331038 AN: 1454756 Hom.: 41288 AF XY: 0.226 AC XY: 163526 AN XY: 723500

Gnomad4 AFR exome AF: 0.0329

Gnomad4 AMR exome AF: 0.116

Gnomad4 ASJ exome AF: 0.193

Gnomad4 EAS exome AF: 0.000530

Gnomad4 SAS exome AF: 0.129

Gnomad4 FIN exome AF: 0.265

Gnomad4 NFE exome AF: 0.254

Gnomad4 OTH exome AF: 0.203

GnomAD4 genome AF: 0.170 AC: 25794 AN: 152022 Hom.: 2926 Cov.: 27 AF XY: 0.167 AC XY: 12424 AN XY: 74308

Gnomad4 AFR AF: 0.0419

Gnomad4 AMR AF: 0.139

Gnomad4 ASJ AF: 0.189

Gnomad4 EAS AF: 0.00231

Gnomad4 SAS AF: 0.109

Gnomad4 FIN AF: 0.265

Gnomad4 NFE AF: 0.255

Gnomad4 OTH AF: 0.171

Alfa AF: 0.212 Hom.: 664

Bravo AF: 0.156

Asia WGS AF: 0.0500 AC: 173 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 29, 2020

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Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs144384652; hg19: chr1-26383645;