Variant 8-66128326-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_184085.2(TRIM55):c.191C>T(p.Thr64Ile) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,458,562 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

TRIM55
NM_184085.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.88

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.20314509).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TRIM55	NM_184085.2 linkuse as main transcript	c.191C>T	p.Thr64Ile	missense_variant	2/10	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.191C>T	p.Thr64Ile	missense_variant	2/10	1	NM_184085.2	ENSP00000323913	A1	Q9BYV6-1
TRIM55	ENST00000276573.11 linkuse as main transcript	c.191C>T	p.Thr64Ile	missense_variant	2/11	1		ENSP00000276573	A1	Q9BYV6-3
TRIM55	ENST00000353317.9 linkuse as main transcript	c.191C>T	p.Thr64Ile	missense_variant	2/9	1		ENSP00000297348	P4	Q9BYV6-2
TRIM55	ENST00000350034.4 linkuse as main transcript	c.191C>T	p.Thr64Ile	missense_variant	2/5	1		ENSP00000332302		Q9BYV6-4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000402

AC:

AN:

248552

Hom.:

AF XY:

0.00

AC XY:

AN XY:

134430

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000549

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:

0.00000137

AC:

AN:

1458562

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

725418

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000253

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000824

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain: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 30, 2023

The c.191C>T (p.T64I) alteration is located in exon 2 (coding exon 2) of the TRIM55 gene. This alteration results from a C to T substitution at nucleotide position 191, causing the threonine (T) at amino acid position 64 to be replaced by an isoleucine (I). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.22

BayesDel_addAF

Benign

-0.25

BayesDel_noAF

Benign

-0.43

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.24

.;T;.;.

Eigen

Benign

-0.23

Eigen_PC

Benign

0.0060

FATHMM_MKL

Uncertain

0.95

LIST_S2

Benign

0.76

T;T;T;T

M_CAP

Benign

0.0078

MetaRNN

Benign

0.20

T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.41

N;N;N;N

MutationTaster

Benign

0.97

D;D;D;D

PrimateAI

Pathogenic

0.82

PROVEAN

Uncertain

-3.4

D;D;D;D

REVEL

Benign

0.051

Sift

Benign

0.046

D;T;T;T

Sift4G

Uncertain

0.030

D;D;D;D

Polyphen

0.0010

B;B;B;B

Vest4

0.48

MutPred

0.43

Loss of glycosylation at T64 (P = 0.0164);Loss of glycosylation at T64 (P = 0.0164);Loss of glycosylation at T64 (P = 0.0164);Loss of glycosylation at T64 (P = 0.0164);

MVP

0.51

MPC

0.046

ClinPred

0.44

GERP RS

4.8

Varity_R

0.33

gMVP

0.51

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