Variant 2-27305029-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_187841.3(TRIM54):c.584T>G(p.Met195Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000777 in 1,613,996 control chromosomes in the GnomAD database, including 1 homozygotes. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00056 ( 0 hom., cov: 31)

Exomes 𝑓: 0.00080 ( 1 hom. )

Consequence

TRIM54
NM_187841.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.89

Variant links:

Genes affected

TRIM54 (HGNC:16008): (tripartite motif containing 54) The protein encoded by this gene contains a RING finger motif and is highly similar to the ring finger proteins RNF28/MURF1 and RNF29/MURF2. In vitro studies demonstrated that this protein, RNF28, and RNF29 form heterodimers, which may be important for the regulation of titin kinase and microtubule-dependent signal pathways in striated muscles. Alternatively spliced transcript variants encoding distinct isoforms have been reported. [provided by RefSeq, Jul 2008]

TRIM54 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TRIM54	NM_187841.3 linkuse as main transcript	c.584T>G	p.Met195Arg	missense_variant	4/9	ENST00000380075.7	NP_912730.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TRIM54	ENST00000380075.7 linkuse as main transcript	c.584T>G	p.Met195Arg	missense_variant	4/9	1	NM_187841.3	ENSP00000369415	P2	Q9BYV2-1
TRIM54	ENST00000296098.4 linkuse as main transcript	c.710T>G	p.Met237Arg	missense_variant	5/10	1		ENSP00000296098	A2	Q9BYV2-2
TRIM54	ENST00000488321.1 linkuse as main transcript	n.339T>G		non_coding_transcript_exon_variant	1/2	2

Frequencies

GnomAD3 genomes

AF:

0.000559

AC:

AN:

152106

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000121

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000589

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.000377

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000956

Gnomad OTH

AF:

0.000479

GnomAD3 exomes

AF:

0.000443

AC:

111

AN:

250654

Hom.:

AF XY:

0.000376

AC XY:

AN XY:

135610

show subpopulations

Gnomad AFR exome

AF:

0.000185

Gnomad AMR exome

AF:

0.000232

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000229

Gnomad FIN exome

AF:

0.000371

Gnomad NFE exome

AF:

0.000724

Gnomad OTH exome

AF:

0.000490

GnomAD4 exome

AF:

0.000800

AC:

1169

AN:

1461772

Hom.:

Cov.:

AF XY:

0.000729

AC XY:

530

AN XY:

727194

show subpopulations

Gnomad4 AFR exome

AF:

0.0000896

Gnomad4 AMR exome

AF:

0.000179

Gnomad4 ASJ exome

AF:

0.0000383

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000162

Gnomad4 FIN exome

AF:

0.000599

Gnomad4 NFE exome

AF:

0.000972

Gnomad4 OTH exome

AF:

0.000480

GnomAD4 genome

AF:

0.000558

AC:

AN:

152224

Hom.:

Cov.:

AF XY:

0.000457

AC XY:

AN XY:

74428

show subpopulations

Gnomad4 AFR

AF:

0.000120

Gnomad4 AMR

AF:

0.000589

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.000377

Gnomad4 NFE

AF:

0.000956

Gnomad4 OTH

AF:

0.000474

Alfa

AF:

0.000631

Hom.:

Bravo

AF:

0.000514

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.000519

AC:

ESP6500AA

AF:

0.000681

AC:

ESP6500EA

AF:

0.00105

AC:

ExAC

AF:

0.000420

AC:

EpiCase

AF:

0.000927

EpiControl

AF:

0.000830

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Feb 01, 2024

TRIM54: PM2:Supporting -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.96

BayesDel_addAF

Benign

-0.068

BayesDel_noAF

Uncertain

0.080

CADD

Pathogenic

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.63

D;.

Eigen

Uncertain

0.58

Eigen_PC

Uncertain

0.63

FATHMM_MKL

Pathogenic

1.0

LIST_S2

Benign

0.80

T;T

M_CAP

Benign

0.033

MetaRNN

Uncertain

0.58

D;D

MetaSVM

Benign

-0.85

MutationAssessor

Uncertain

2.4

M;.

MutationTaster

Benign

1.0

D;D

PrimateAI

Pathogenic

0.81

PROVEAN

Pathogenic

-4.4

D;D

REVEL

Uncertain

0.44

Sift

Pathogenic

0.0

D;D

Sift4G

Pathogenic

0.0010

D;D

Polyphen

0.93

P;D

Vest4

0.84

MVP

0.76

MPC

0.47

ClinPred

0.15

GERP RS

5.6

Varity_R

0.94

gMVP

0.92

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