Variant 8-66135006-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_184085.2(TRIM55):c.358G>T(p.Asp120Tyr) variant causes a missense change. The variant allele was found at a frequency of 0.000802 in 1,613,930 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00060 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00082 ( 7 hom. )

Consequence

TRIM55
NM_184085.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1B:1

Conservation

PhyloP100: 5.18

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 Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.03018856).

BS2

High Homozygotes in GnomAdExome4 at 7 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TRIM55	NM_184085.2 linkuse as main transcript	c.358G>T	p.Asp120Tyr	missense_variant	3/10	ENST00000315962.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TRIM55	ENST00000315962.9 linkuse as main transcript	c.358G>T	p.Asp120Tyr	missense_variant	3/10	1	NM_184085.2	A1	Q9BYV6-1
TRIM55	ENST00000276573.11 linkuse as main transcript	c.358G>T	p.Asp120Tyr	missense_variant	3/11	1		A1	Q9BYV6-3
TRIM55	ENST00000353317.9 linkuse as main transcript	c.358G>T	p.Asp120Tyr	missense_variant	3/9	1		P4	Q9BYV6-2
TRIM55	ENST00000350034.4 linkuse as main transcript	c.358G>T	p.Asp120Tyr	missense_variant	3/5	1			Q9BYV6-4

Frequencies

GnomAD3 genomes

AF:

0.000605

AC:

AN:

152120

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000966

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000655

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00249

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000941

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000673

AC:

169

AN:

251148

Hom.:

AF XY:

0.000759

AC XY:

103

AN XY:

135748

show subpopulations

Gnomad AFR exome

AF:

0.0000615

Gnomad AMR exome

AF:

0.000116

Gnomad ASJ exome

AF:

0.000199

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00180

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000916

Gnomad OTH exome

AF:

0.000490

GnomAD4 exome

AF:

0.000822

AC:

1202

AN:

1461692

Hom.:

Cov.:

AF XY:

0.000875

AC XY:

636

AN XY:

727156

show subpopulations

Gnomad4 AFR exome

AF:

0.000120

Gnomad4 AMR exome

AF:

0.000179

Gnomad4 ASJ exome

AF:

0.000230

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00167

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000883

Gnomad4 OTH exome

AF:

0.000762

GnomAD4 genome

AF:

0.000604

AC:

AN:

152238

Hom.:

Cov.:

AF XY:

0.000578

AC XY:

AN XY:

74434

show subpopulations

Gnomad4 AFR

AF:

0.0000963

Gnomad4 AMR

AF:

0.000654

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00249

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000941

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.000854

Hom.:

Bravo

AF:

0.000680

TwinsUK

AF:

0.000809

AC:

ALSPAC

AF:

0.000519

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.00186

AC:

ExAC

AF:

0.000651

AC:

EpiCase

AF:

0.00120

EpiControl

AF:

0.00107

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 14, 2021

The c.358G>T (p.D120Y) alteration is located in exon 3 (coding exon 3) of the TRIM55 gene. This alteration results from a G to T substitution at nucleotide position 358, causing the aspartic acid (D) at amino acid position 120 to be replaced by a tyrosine (Y). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

TRIM55-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Jan 31, 2023

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

0.21

BayesDel_addAF

Benign

-0.38

BayesDel_noAF

Benign

-0.33

CADD

Pathogenic

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.53

.;D;.;.

Eigen

Uncertain

0.37

Eigen_PC

Uncertain

0.43

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.86

D;D;T;T

M_CAP

Benign

0.036

MetaRNN

Benign

0.030

T;T;T;T

MetaSVM

Benign

-0.76

MutationAssessor

Benign

1.7

L;L;L;L

MutationTaster

Benign

1.0

D;D;D;D

PrimateAI

Benign

0.43

PROVEAN

Uncertain

-3.3

D;D;D;D

REVEL

Benign

0.18

Sift

Uncertain

0.0040

D;D;D;D

Sift4G

Uncertain

0.0020

D;D;D;D

Polyphen

0.62

P;P;B;P

Vest4

0.58

MVP

0.54

MPC

0.28

ClinPred

0.15

GERP RS

5.5

Varity_R

0.60

gMVP

0.50

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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