chr1-26057154-CCAGGGGT-C

Variant names:

• chr1-26057154-CCAGGGGT-C
• rs144384652
• NM_032588.4:c.979+42_979+48delACCCCTG

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_032588.4(TRIM63):​c.979+42_979+48delACCCCTG 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
• Publications: 0 publications found

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 Gene-Disease associations (from GenCC):

• hypertrophic cardiomyopathy

  Inheritance: AR, AD Classification: MODERATE, NO_KNOWN Submitted by: ClinGen, Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032588.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRIM63	NM_032588.4	MANE Select	c.979+42_979+48delACCCCTG		intron	N/A	NP_115977.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRIM63	ENST00000374272.4	TSL:1 MANE Select	c.979+42_979+48delACCCCTG		intron	N/A	ENSP00000363390.3	Q969Q1-1

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

GnomAD2 exomes AF: 0.181 AC: 44901 AN: 247648 AF XY: 0.185

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 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

African (AFR) AF: 0.0329 AC: 1099 AN: 33354

American (AMR) AF: 0.116 AC: 5140 AN: 44424

Ashkenazi Jewish (ASJ) AF: 0.193 AC: 4993 AN: 25912

East Asian (EAS) AF: 0.000530 AC: 21 AN: 39602

South Asian (SAS) AF: 0.129 AC: 11043 AN: 85826

European-Finnish (FIN) AF: 0.265 AC: 14051 AN: 53040

Middle Eastern (MID) AF: 0.179 AC: 1027 AN: 5738

European-Non Finnish (NFE) AF: 0.254 AC: 281487 AN: 1106742

Other (OTH) AF: 0.203 AC: 12177 AN: 60118

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

African (AFR) AF: 0.0419 AC: 1740 AN: 41526

American (AMR) AF: 0.139 AC: 2128 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.189 AC: 656 AN: 3466

East Asian (EAS) AF: 0.00231 AC: 12 AN: 5184

South Asian (SAS) AF: 0.109 AC: 525 AN: 4826

European-Finnish (FIN) AF: 0.265 AC: 2797 AN: 10560

Middle Eastern (MID) AF: 0.194 AC: 57 AN: 294

European-Non Finnish (NFE) AF: 0.255 AC: 17281 AN: 67876

Other (OTH) AF: 0.171 AC: 362 AN: 2112

Alfa AF: 0.212 Hom.: 664

Bravo AF: 0.156

Asia WGS AF: 0.0500 AC: 173 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.2
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs144384652; hg19: chr1-26383645;