Variant 8-66137119-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_184085.2(TRIM55):c.532A>G(p.Ile178Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000015 in 1,461,826 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.000015 ( 0 hom. )

Consequence

TRIM55
NM_184085.2 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.02

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 -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.04453087).

BP6

Variant 8-66137119-A-G is Benign according to our data. Variant chr8-66137119-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 3328828.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TRIM55	NM_184085.2 linkuse as main transcript	c.532A>G	p.Ile178Val	missense_variant	4/10	ENST00000315962.9	NP_908973.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TRIM55	ENST00000315962.9 linkuse as main transcript	c.532A>G	p.Ile178Val	missense_variant	4/10	1	NM_184085.2	ENSP00000323913	A1	Q9BYV6-1
TRIM55	ENST00000276573.11 linkuse as main transcript	c.532A>G	p.Ile178Val	missense_variant	4/11	1		ENSP00000276573	A1	Q9BYV6-3
TRIM55	ENST00000353317.9 linkuse as main transcript	c.532A>G	p.Ile178Val	missense_variant	4/9	1		ENSP00000297348	P4	Q9BYV6-2
TRIM55	ENST00000350034.4 linkuse as main transcript	c.532A>G	p.Ile178Val	missense_variant	4/5	1		ENSP00000332302		Q9BYV6-4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000398

AC:

AN:

251246

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135784

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000880

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000150

AC:

AN:

1461826

Hom.:

Cov.:

AF XY:

0.00000963

AC XY:

AN XY:

727206

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000171

Gnomad4 OTH exome

AF:

0.0000331

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

ExAC

AF:

0.00000824

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 06, 2024

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.060

BayesDel_addAF

Benign

-0.35

BayesDel_noAF

Benign

-0.75

CADD

Benign

1.1

DANN

Benign

0.75

DEOGEN2

Benign

0.089

.;T;.;.

Eigen

Benign

-0.97

Eigen_PC

Benign

-0.78

FATHMM_MKL

Benign

0.44

LIST_S2

Benign

0.59

T;T;T;T

M_CAP

Benign

0.0045

MetaRNN

Benign

0.045

T;T;T;T

MetaSVM

Benign

-0.98

MutationAssessor

Benign

-0.66

N;N;N;N

MutationTaster

Benign

1.0

N;N;N;N

PrimateAI

Benign

0.31

PROVEAN

Benign

0.020

N;N;N;N

REVEL

Benign

0.063

Sift

Benign

0.93

T;T;T;T

Sift4G

Benign

0.65

T;T;T;T

Polyphen

0.0

B;B;B;B

Vest4

0.20

MutPred

0.33

Loss of stability (P = 0.1897);Loss of stability (P = 0.1897);Loss of stability (P = 0.1897);Loss of stability (P = 0.1897);

MVP

0.17

MPC

0.034

ClinPred

0.041

GERP RS

2.5

Varity_R

0.022

gMVP

0.17

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