rs139128442

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_187841.3(TRIM54):ā€‹c.584T>Cā€‹(p.Met195Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,774 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 31)
Exomes š‘“: 6.8e-7 ( 0 hom. )

Consequence

TRIM54
NM_187841.3 missense

Scores

3
4
12

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 7.89
Variant links:
Genes affected
TRIM54 (HGNC:16008): (tripartite motif containing 54) The protein encoded by this gene contains a RING finger motif and is highly similar to the ring finger proteins RNF28/MURF1 and RNF29/MURF2. In vitro studies demonstrated that this protein, RNF28, and RNF29 form heterodimers, which may be important for the regulation of titin kinase and microtubule-dependent signal pathways in striated muscles. Alternatively spliced transcript variants encoding distinct isoforms have been reported. [provided by RefSeq, Jul 2008]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.37830085).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
TRIM54NM_187841.3 linkc.584T>C p.Met195Thr missense_variant Exon 4 of 9 ENST00000380075.7 NP_912730.2 Q9BYV2-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
TRIM54ENST00000380075.7 linkc.584T>C p.Met195Thr missense_variant Exon 4 of 9 1 NM_187841.3 ENSP00000369415.3 Q9BYV2-1
TRIM54ENST00000296098.4 linkc.710T>C p.Met237Thr missense_variant Exon 5 of 10 1 ENSP00000296098.4 Q9BYV2-2
TRIM54ENST00000488321.1 linkn.339T>C non_coding_transcript_exon_variant Exon 1 of 2 2

Frequencies

GnomAD3 genomes
Cov.:
31
GnomAD3 exomes
AF:
0.00000399
AC:
1
AN:
250654
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
135610
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.0000544
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
6.84e-7
AC:
1
AN:
1461774
Hom.:
0
Cov.:
30
AF XY:
0.00
AC XY:
0
AN XY:
727196
show subpopulations
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.:
31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.82
BayesDel_addAF
Uncertain
0.093
D
BayesDel_noAF
Benign
-0.10
CADD
Uncertain
25
DANN
Benign
0.95
DEOGEN2
Uncertain
0.62
D;.
Eigen
Benign
0.10
Eigen_PC
Uncertain
0.30
FATHMM_MKL
Pathogenic
1.0
D
LIST_S2
Benign
0.71
T;T
M_CAP
Benign
0.018
T
MetaRNN
Benign
0.38
T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
1.8
L;.
PrimateAI
Pathogenic
0.84
D
PROVEAN
Uncertain
-3.7
D;D
REVEL
Benign
0.28
Sift
Benign
0.11
T;T
Sift4G
Benign
0.15
T;T
Polyphen
0.024
B;B
Vest4
0.68
MutPred
0.39
Loss of catalytic residue at V191 (P = 0.0376);.;
MVP
0.66
MPC
0.19
ClinPred
0.93
D
GERP RS
5.6
Varity_R
0.55
gMVP
0.80

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs139128442; hg19: chr2-27527897; API