dbSNP rs61760894: TRIM55:p.Pro60Gln (chr8-66128314-C-A) – ACMG Classification: Uncertain_significance (3 pts)

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

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]

TRIM55 links:

Genome browser will be placed here

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
TRIM55	NM_184085.2 link	c.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	UniProt
TRIM55	ENST00000315962.9 link	c.179C>A	p.Pro60Gln	missense_variant	Exon 2 of 10	1	NM_184085.2	ENSP00000323913.4	Q9BYV6-1
TRIM55	ENST00000276573.11 link	c.179C>A	p.Pro60Gln	missense_variant	Exon 2 of 11	1		ENSP00000276573.7	Q9BYV6-3
TRIM55	ENST00000353317.9 link	c.179C>A	p.Pro60Gln	missense_variant	Exon 2 of 9	1		ENSP00000297348.8	Q9BYV6-2
TRIM55	ENST00000350034.4 link	c.179C>A	p.Pro60Gln	missense_variant	Exon 2 of 5	1		ENSP00000332302.4	Q9BYV6-4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000410

AC:

AN:

243708

Hom.:

AF XY:

0.00

AC XY:

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:

AN:

1451870

Hom.:

Cov.:

AF XY:

0.00000277

AC XY:

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.:

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

BayesDel_noAF

Benign

-0.11

CADD

Pathogenic

DANN

Uncertain

0.99

DEOGEN2

Benign

0.30

.;T;.;.

Eigen

Uncertain

0.62

Eigen_PC

Pathogenic

0.69

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.88

D;D;D;D

M_CAP

Benign

0.066

MetaRNN

Pathogenic

0.82

D;D;D;D

MetaSVM

Benign

-0.80

MutationAssessor

Benign

0.34

N;N;N;N

PrimateAI

Pathogenic

0.84

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

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over