Variant 8-66149745-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2BP4_StrongBP6

The NM_184085.2(TRIM55):c.704G>A(p.Arg235Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000245 in 1,614,118 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

Frequency

Genomes: 𝑓 0.0012 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00014 ( 0 hom. )

Consequence

TRIM55
NM_184085.2 missense

Scores

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: 2.52

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 Likely_benign. Variant got -3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.0061166584).

BP6

Variant 8-66149745-G-A is Benign according to our data. Variant chr8-66149745-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 3051012.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TRIM55	NM_184085.2 linkuse as main transcript	c.704G>A	p.Arg235Gln	missense_variant	5/10	ENST00000315962.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TRIM55	ENST00000315962.9 linkuse as main transcript	c.704G>A	p.Arg235Gln	missense_variant	5/10	1	NM_184085.2	A1	Q9BYV6-1
TRIM55	ENST00000276573.11 linkuse as main transcript	c.704G>A	p.Arg235Gln	missense_variant	5/11	1		A1	Q9BYV6-3
TRIM55	ENST00000353317.9 linkuse as main transcript	c.704G>A	p.Arg235Gln	missense_variant	5/9	1		P4	Q9BYV6-2
TRIM55	ENST00000350034.4 linkuse as main transcript	c.603+12555G>A		intron_variant		1			Q9BYV6-4

Frequencies

GnomAD3 genomes

AF:

0.00123

AC:

187

AN:

152206

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00425

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000393

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00143

GnomAD3 exomes

AF:

0.000354

AC:

AN:

251398

Hom.:

AF XY:

0.000280

AC XY:

AN XY:

135878

show subpopulations

Gnomad AFR exome

AF:

0.00394

Gnomad AMR exome

AF:

0.000318

Gnomad ASJ exome

AF:

0.000695

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000440

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.000142

AC:

208

AN:

1461794

Hom.:

Cov.:

AF XY:

0.000127

AC XY:

AN XY:

727200

show subpopulations

Gnomad4 AFR exome

AF:

0.00421

Gnomad4 AMR exome

AF:

0.000313

Gnomad4 ASJ exome

AF:

0.000536

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000348

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000180

Gnomad4 OTH exome

AF:

0.000248

GnomAD4 genome

AF:

0.00123

AC:

188

AN:

152324

Hom.:

Cov.:

AF XY:

0.00102

AC XY:

AN XY:

74492

show subpopulations

Gnomad4 AFR

AF:

0.00426

Gnomad4 AMR

AF:

0.000392

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.000153

Hom.:

Bravo

AF:

0.00129

ESP6500AA

AF:

0.00363

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000404

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

TRIM55-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Apr 21, 2022

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.090

BayesDel_addAF

Benign

-0.55

BayesDel_noAF

Benign

-0.56

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.090

.;T;.

Eigen

Benign

-0.014

Eigen_PC

Benign

0.11

FATHMM_MKL

Benign

0.74

LIST_S2

Benign

0.76

T;T;T

M_CAP

Benign

0.011

MetaRNN

Benign

0.0061

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.6

L;L;L

MutationTaster

Benign

1.0

N;N;N;N

PrimateAI

Benign

0.44

PROVEAN

Benign

-0.63

N;N;N

REVEL

Benign

0.072

Sift

Benign

0.32

T;T;T

Sift4G

Benign

0.30

T;T;T

Polyphen

0.26

B;B;B

Vest4

0.36

MVP

0.38

MPC

0.064

ClinPred

0.020

GERP RS

5.4

Varity_R

0.11

gMVP

0.32

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over