dbSNP rs61760894: TRIM55:p.Pro60Gln (chr8-66128314-C-A) – ACMG Classification: Uncertain_significance (3 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2PP3

The NM_184085.2(TRIM55):c.179C>A(p.Pro60Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000276 in 1,451,870 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P60L) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000028 ( 0 hom. )

Consequence

TRIM55
NM_184085.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 7.71

Publications

2 publications found

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 was made for transcript

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.823

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_184085.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TRIM55	NM_184085.2	MANE Select	c.179C>A	p.Pro60Gln	missense	Exon 2 of 10	NP_908973.1	Q9BYV6-1
TRIM55	NM_033058.3		c.179C>A	p.Pro60Gln	missense	Exon 2 of 11	NP_149047.2
TRIM55	NM_184086.2		c.179C>A	p.Pro60Gln	missense	Exon 2 of 9	NP_908974.1	Q9BYV6-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TRIM55	ENST00000315962.9	TSL:1 MANE Select	c.179C>A	p.Pro60Gln	missense	Exon 2 of 10	ENSP00000323913.4	Q9BYV6-1
TRIM55	ENST00000276573.11	TSL:1	c.179C>A	p.Pro60Gln	missense	Exon 2 of 11	ENSP00000276573.7	Q9BYV6-3
TRIM55	ENST00000353317.9	TSL:1	c.179C>A	p.Pro60Gln	missense	Exon 2 of 9	ENSP00000297348.8	Q9BYV6-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000410

AC:

AN:

243708

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000558

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000276

AC:

AN:

1451870

Hom.:

Cov.:

AF XY:

0.00000277

AC XY:

AN XY:

721778

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32944

American (AMR)

AF:

0.00

AC:

AN:

42060

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25706

East Asian (EAS)

AF:

0.000101

AC:

AN:

39436

South Asian (SAS)

AF:

0.00

AC:

AN:

85108

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53334

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5718

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1107602

Other (OTH)

AF:

0.00

AC:

AN:

59962

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000113

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.66

BayesDel_addAF

Benign

-0.031

BayesDel_noAF

Benign

-0.11

CADD

Pathogenic

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.30

Eigen

Uncertain

0.62

Eigen_PC

Pathogenic

0.69

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.88

M_CAP

Benign

0.066

MetaRNN

Pathogenic

0.82

MetaSVM

Benign

-0.80

MutationAssessor

Benign

0.34

PhyloP100

7.7

PrimateAI

Pathogenic

0.84

PROVEAN

Pathogenic

-5.6

REVEL

Uncertain

0.34

Sift

Uncertain

0.0010

Sift4G

Uncertain

0.0020

Polyphen

0.99

Vest4

0.74

MutPred

0.72

Loss of glycosylation at P60 (P = 0.0883)

MVP

0.56

MPC

0.27

ClinPred

0.98

GERP RS

5.7

Varity_R

0.57

gMVP

0.52

Mutation Taster

=25/75

disease causing

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over