rs61760894

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_184085.2(TRIM55):​c.179C>A​(p.Pro60Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000276 in 1,451,870 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P60L) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000028 ( 0 hom. )

Consequence

TRIM55
NM_184085.2 missense

Scores

6
6
7

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 7.71
Variant links:
Genes affected
TRIM55 (HGNC:14215): (tripartite motif containing 55) The protein encoded by this gene contains a RING zinc finger, a motif known to be involved in protein-protein interactions. This protein associates transiently with microtubules, myosin, and titin during muscle sarcomere assembly. It may act as a transient adaptor and plays a regulatory role in the assembly of sarcomeres. Four alternatively spliced transcript variants encoding distinct isoforms have been described. [provided by RefSeq, Jul 2008]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.823

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
TRIM55NM_184085.2 linkc.179C>A p.Pro60Gln missense_variant Exon 2 of 10 ENST00000315962.9 NP_908973.1 Q9BYV6-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
TRIM55ENST00000315962.9 linkc.179C>A p.Pro60Gln missense_variant Exon 2 of 10 1 NM_184085.2 ENSP00000323913.4 Q9BYV6-1
TRIM55ENST00000276573.11 linkc.179C>A p.Pro60Gln missense_variant Exon 2 of 11 1 ENSP00000276573.7 Q9BYV6-3
TRIM55ENST00000353317.9 linkc.179C>A p.Pro60Gln missense_variant Exon 2 of 9 1 ENSP00000297348.8 Q9BYV6-2
TRIM55ENST00000350034.4 linkc.179C>A p.Pro60Gln missense_variant Exon 2 of 5 1 ENSP00000332302.4 Q9BYV6-4

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.00000410
AC:
1
AN:
243708
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
132044
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.0000558
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:
0.00000276
AC:
4
AN:
1451870
Hom.:
0
Cov.:
30
AF XY:
0.00000277
AC XY:
2
AN XY:
721778
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.000101
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
Bravo
AF:
0.0000113

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.66
BayesDel_addAF
Benign
-0.031
T
BayesDel_noAF
Benign
-0.11
CADD
Pathogenic
31
DANN
Uncertain
0.99
DEOGEN2
Benign
0.30
.;T;.;.
Eigen
Uncertain
0.62
Eigen_PC
Pathogenic
0.69
FATHMM_MKL
Pathogenic
0.98
D
LIST_S2
Uncertain
0.88
D;D;D;D
M_CAP
Benign
0.066
D
MetaRNN
Pathogenic
0.82
D;D;D;D
MetaSVM
Benign
-0.80
T
MutationAssessor
Benign
0.34
N;N;N;N
PrimateAI
Pathogenic
0.84
D
PROVEAN
Pathogenic
-5.6
D;D;D;D
REVEL
Uncertain
0.34
Sift
Uncertain
0.0010
D;D;D;D
Sift4G
Uncertain
0.0020
D;D;D;T
Polyphen
0.99
D;D;D;D
Vest4
0.74
MutPred
0.72
Loss of glycosylation at P60 (P = 0.0883);Loss of glycosylation at P60 (P = 0.0883);Loss of glycosylation at P60 (P = 0.0883);Loss of glycosylation at P60 (P = 0.0883);
MVP
0.56
MPC
0.27
ClinPred
0.98
D
GERP RS
5.7
Varity_R
0.57
gMVP
0.52

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.050
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: rs61760894; hg19: chr8-67040549; API