rs140523053
Positions:
Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4BS2
The NM_032588.4(TRIM63):c.143C>T(p.Ala48Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0022 in 1,614,000 control chromosomes in the GnomAD database, including 8 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).
Frequency
Genomes: 𝑓 0.0013 ( 0 hom., cov: 31)
Exomes 𝑓: 0.0023 ( 8 hom. )
Consequence
TRIM63
NM_032588.4 missense
NM_032588.4 missense
Scores
5
7
7
Clinical Significance
Conservation
PhyloP100: 9.99
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]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -5 ACMG points.
BP4
?
Computational evidence support a benign effect (MetaRNN=0.29423878).
BS2
?
High Homozygotes in GnomAdExome4 at 8 gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TRIM63 | NM_032588.4 | c.143C>T | p.Ala48Val | missense_variant | 1/9 | ENST00000374272.4 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TRIM63 | ENST00000374272.4 | c.143C>T | p.Ala48Val | missense_variant | 1/9 | 1 | NM_032588.4 | P1 | |
TRIM63 | ENST00000483052.1 | n.1085C>T | non_coding_transcript_exon_variant | 1/3 | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.00127 AC: 193AN: 152166Hom.: 0 Cov.: 31
GnomAD3 genomes
?
AF:
AC:
193
AN:
152166
Hom.:
Cov.:
31
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD3 exomes AF: 0.00138 AC: 345AN: 250842Hom.: 2 AF XY: 0.00157 AC XY: 213AN XY: 135562
GnomAD3 exomes
AF:
AC:
345
AN:
250842
Hom.:
AF XY:
AC XY:
213
AN XY:
135562
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad SAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.00230 AC: 3355AN: 1461716Hom.: 8 Cov.: 30 AF XY: 0.00233 AC XY: 1693AN XY: 727140
GnomAD4 exome
AF:
AC:
3355
AN:
1461716
Hom.:
Cov.:
30
AF XY:
AC XY:
1693
AN XY:
727140
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome ? AF: 0.00127 AC: 193AN: 152284Hom.: 0 Cov.: 31 AF XY: 0.00129 AC XY: 96AN XY: 74466
GnomAD4 genome
?
AF:
AC:
193
AN:
152284
Hom.:
Cov.:
31
AF XY:
AC XY:
96
AN XY:
74466
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
Alfa
AF:
Hom.:
Bravo
AF:
TwinsUK
AF:
AC:
7
ALSPAC
AF:
AC:
15
ESP6500AA
AF:
AC:
1
ESP6500EA
AF:
AC:
17
ExAC
?
AF:
AC:
152
Asia WGS
AF:
AC:
2
AN:
3478
EpiCase
AF:
EpiControl
AF:
ClinVar
Significance: Likely benign
Submissions summary: Benign:4
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Benign:3
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | May 01, 2024 | TRIM63: BS2 - |
Likely benign, no assertion criteria provided | clinical testing | Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center | - | - - |
Likely benign, no assertion criteria provided | clinical testing | Genome Diagnostics Laboratory, University Medical Center Utrecht | - | - - |
Primary familial hypertrophic cardiomyopathy Benign:1
Likely benign, no assertion criteria provided | clinical testing | Blueprint Genetics | Jul 21, 2014 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Benign
T
BayesDel_noAF
Uncertain
CADD
Pathogenic
DANN
Pathogenic
DEOGEN2
Benign
T
Eigen
Uncertain
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D
M_CAP
Benign
T
MetaRNN
Benign
T
MetaSVM
Benign
T
MutationAssessor
Benign
N
MutationTaster
Benign
D
PrimateAI
Uncertain
T
PROVEAN
Uncertain
D
REVEL
Uncertain
Sift
Pathogenic
D
Sift4G
Uncertain
T
Polyphen
D
Vest4
MVP
MPC
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at