Variant 8-66149676-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_184085.2(TRIM55):c.635G>A(p.Cys212Tyr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,762 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.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

TRIM55
NM_184085.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 8.01

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 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.822

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TRIM55	NM_184085.2 linkuse as main transcript	c.635G>A	p.Cys212Tyr	missense_variant	5/10	ENST00000315962.9	NP_908973.1	Q9BYV6-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
TRIM55	ENST00000315962.9 linkuse as main transcript	c.635G>A	p.Cys212Tyr	missense_variant	5/10	1	NM_184085.2	ENSP00000323913.4	Q9BYV6-1
TRIM55	ENST00000276573.11 linkuse as main transcript	c.635G>A	p.Cys212Tyr	missense_variant	5/11	1		ENSP00000276573.7	Q9BYV6-3
TRIM55	ENST00000353317.9 linkuse as main transcript	c.635G>A	p.Cys212Tyr	missense_variant	5/9	1		ENSP00000297348.8	Q9BYV6-2
TRIM55	ENST00000350034.4 linkuse as main transcript	c.603+12486G>A		intron_variant		1		ENSP00000332302.4	Q9BYV6-4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461762

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727192

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

8.99e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000756

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

Nov 08, 2024

The c.635G>A (p.C212Y) alteration is located in exon 5 (coding exon 5) of the TRIM55 gene. This alteration results from a G to A substitution at nucleotide position 635, causing the cysteine (C) at amino acid position 212 to be replaced by a tyrosine (Y). 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

Pathogenic

0.74

BayesDel_addAF

Pathogenic

0.22

BayesDel_noAF

Uncertain

0.070

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.63

.;D;.

Eigen

Pathogenic

0.83

Eigen_PC

Pathogenic

0.81

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.91

D;D;D

M_CAP

Benign

0.038

MetaRNN

Pathogenic

0.82

D;D;D

MetaSVM

Benign

-0.76

MutationAssessor

Uncertain

2.9

M;M;M

PrimateAI

Pathogenic

0.87

PROVEAN

Pathogenic

-6.2

D;D;D

REVEL

Uncertain

0.43

Sift

Uncertain

0.010

D;D;D

Sift4G

Benign

0.099

T;T;T

Polyphen

0.99

D;D;D

Vest4

0.82

MutPred

0.27

Loss of methylation at K214 (P = 0.0836);Loss of methylation at K214 (P = 0.0836);Loss of methylation at K214 (P = 0.0836);

MVP

0.47

MPC

0.34

ClinPred

1.0

GERP RS

5.4

Varity_R

0.68

gMVP

0.59

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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