NM_032588.4:c.979+76G>C

Variant names:

• chr1-26057127-C-G
• rs1317428
• NM_032588.4:c.979+76G>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 1 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 -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 VariationId 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.

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+76G>C		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+76G>C		intron	N/A	ENSP00000363390.3	Q969Q1-1

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

African (AFR) AF: 0.299 AC: 9642 AN: 32194

American (AMR) AF: 0.0202 AC: 838 AN: 41510

Ashkenazi Jewish (ASJ) AF: 0.000808 AC: 20 AN: 24760

East Asian (EAS) AF: 0.00 AC: 0 AN: 39252

South Asian (SAS) AF: 0.00108 AC: 90 AN: 83020

European-Finnish (FIN) AF: 0.0000195 AC: 1 AN: 51382

Middle Eastern (MID) AF: 0.0199 AC: 111 AN: 5582

European-Non Finnish (NFE) AF: 0.00140 AC: 1513 AN: 1082868

Other (OTH) AF: 0.0236 AC: 1384 AN: 58700

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

African (AFR) AF: 0.293 AC: 12149 AN: 41426

American (AMR) AF: 0.0362 AC: 549 AN: 15182

Ashkenazi Jewish (ASJ) AF: 0.000289 AC: 1 AN: 3456

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5182

South Asian (SAS) AF: 0.00208 AC: 10 AN: 4804

European-Finnish (FIN) AF: 0.0000965 AC: 1 AN: 10368

Middle Eastern (MID) AF: 0.0272 AC: 8 AN: 294

European-Non Finnish (NFE) AF: 0.00260 AC: 175 AN: 67420

Other (OTH) AF: 0.0611 AC: 128 AN: 2096

Alfa AF: 0.00380 Hom.: 6

Bravo AF: 0.0977

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.19
DANN	Benign	0.69
PhyloP100		-1.0
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1317428; hg19: chr1-26383618;