NM_032588.4:c.895G>C

Variant names:

• chr1-26057287-C-G
• NM_032588.4:c.895G>C

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_032588.4(TRIM63):​c.895G>C​(p.Glu299Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: TRIM63 NM_032588.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.04
• 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: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.31943315).

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.895G>C	p.Glu299Gln	missense	Exon 7 of 9	NP_115977.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRIM63	ENST00000374272.4	TSL:1 MANE Select	c.895G>C	p.Glu299Gln	missense	Exon 7 of 9	ENSP00000363390.3	Q969Q1-1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	Inborn genetic diseases (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.67	D
Eigen	Uncertain	0.34
Eigen_PC	Uncertain	0.46
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.81	T
M_CAP	Benign	0.015	T
MetaRNN	Benign	0.32	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.6	M
PhyloP100		3.0
PrimateAI	Benign	0.46	T
PROVEAN	Uncertain	-2.7	D
REVEL	Benign	0.16
Sift	Benign	0.041	D
Sift4G	Uncertain	0.036	D
Polyphen		0.44	B
Vest4		0.39
MutPred		0.59		Loss of ubiquitination at K297 (P = 0.1287)
MVP		0.60
MPC		0.64
ClinPred		0.82	D
GERP RS		5.8
Varity_R		0.42
gMVP		0.24
Mutation Taster		=79/21	polymorphism

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

hg19: chr1-26383778;