NM_032588.4:c.900G>T

Variant names:

• chr1-26057282-C-A
• NM_032588.4:c.900G>T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_032588.4(TRIM63):​c.900G>T​(p.Gln300His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,870 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: TRIM63 NM_032588.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.455

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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.0833447).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRIM63	NM_032588.4	c.900G>T	p.Gln300His	missense_variant	Exon 7 of 9	ENST00000374272.4	NP_115977.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TRIM63	ENST00000374272.4	c.900G>T	p.Gln300His	missense_variant	Exon 7 of 9	1	NM_032588.4	ENSP00000363390.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461870 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 727240

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.64
CADD	Benign	13
DANN	Benign	0.26
DEOGEN2	Benign	0.16	T
Eigen	Benign	-0.89
Eigen_PC	Benign	-0.77
FATHMM_MKL	Benign	0.20	N
LIST_S2	Benign	0.62	T
M_CAP	Benign	0.0044	T
MetaRNN	Benign	0.083	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.1	L
PrimateAI	Benign	0.39	T
PROVEAN	Benign	-1.0	N
REVEL	Benign	0.059
Sift	Benign	0.76	T
Sift4G	Benign	0.58	T
Polyphen		0.0	B
Vest4		0.28
MutPred		0.30		Gain of catalytic residue at G301 (P = 0.0846);
MVP		0.26
MPC		0.16
ClinPred		0.088	T
GERP RS		1.4
Varity_R		0.061
gMVP		0.20

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-26383773;