Variant 2-27282890-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_ModerateBP6BP7BA1

The ENST00000380075.7(TRIM54):c.159C>T(p.Asp53Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0562 in 1,611,688 control chromosomes in the GnomAD database, including 3,006 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.046 ( 223 hom., cov: 32)

Exomes 𝑓: 0.057 ( 2783 hom. )

Consequence

TRIM54
ENST00000380075.7 synonymous

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: -0.933

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.43).

BP6

Variant 2-27282890-C-T is Benign according to our data. Variant chr2-27282890-C-T is described in ClinVar as [Benign]. Clinvar id is 3055449.Status of the report is no_assertion_criteria_provided, 0 stars.

BP7

Synonymous conserved (PhyloP=-0.933 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.065 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TRIM54	NM_187841.3 linkuse as main transcript	c.159C>T	p.Asp53Asp	synonymous_variant	1/9	ENST00000380075.7	NP_912730.2	Q9BYV2-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TRIM54	ENST00000380075.7 linkuse as main transcript	c.159C>T	p.Asp53Asp	synonymous_variant	1/9	1	NM_187841.3	ENSP00000369415.3		Q9BYV2-1
TRIM54	ENST00000296098.4 linkuse as main transcript	c.159C>T	p.Asp53Asp	synonymous_variant	1/10	1		ENSP00000296098.4		Q9BYV2-2

Frequencies

GnomAD3 genomes

AF:

0.0458

AC:

6973

AN:

152224

Hom.:

225

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0116

Gnomad AMI

AF:

0.0943

Gnomad AMR

AF:

0.0393

Gnomad ASJ

AF:

0.113

Gnomad EAS

AF:

0.000962

Gnomad SAS

AF:

0.00434

Gnomad FIN

AF:

0.0685

Gnomad MID

AF:

0.0411

Gnomad NFE

AF:

0.0666

Gnomad OTH

AF:

0.0530

GnomAD3 exomes

AF:

0.0457

AC:

11324

AN:

247974

Hom.:

421

AF XY:

0.0455

AC XY:

6097

AN XY:

133906

show subpopulations

Gnomad AFR exome

AF:

0.0108

Gnomad AMR exome

AF:

0.0260

Gnomad ASJ exome

AF:

0.105

Gnomad EAS exome

AF:

0.000436

Gnomad SAS exome

AF:

0.00514

Gnomad FIN exome

AF:

0.0607

Gnomad NFE exome

AF:

0.0667

Gnomad OTH exome

AF:

0.0522

GnomAD4 exome

AF:

0.0573

AC:

83653

AN:

1459346

Hom.:

2783

Cov.:

AF XY:

0.0561

AC XY:

40748

AN XY:

725868

show subpopulations

Gnomad4 AFR exome

AF:

0.00819

Gnomad4 AMR exome

AF:

0.0270

Gnomad4 ASJ exome

AF:

0.103

Gnomad4 EAS exome

AF:

0.000403

Gnomad4 SAS exome

AF:

0.00554

Gnomad4 FIN exome

AF:

0.0590

Gnomad4 NFE exome

AF:

0.0653

Gnomad4 OTH exome

AF:

0.0513

GnomAD4 genome

AF:

0.0458

AC:

6971

AN:

152342

Hom.:

223

Cov.:

AF XY:

0.0453

AC XY:

3375

AN XY:

74502

show subpopulations

Gnomad4 AFR

AF:

0.0116

Gnomad4 AMR

AF:

0.0393

Gnomad4 ASJ

AF:

0.113

Gnomad4 EAS

AF:

0.000964

Gnomad4 SAS

AF:

0.00435

Gnomad4 FIN

AF:

0.0685

Gnomad4 NFE

AF:

0.0666

Gnomad4 OTH

AF:

0.0525

Alfa

AF:

0.0633

Hom.:

555

Bravo

AF:

0.0421

Asia WGS

AF:

0.00433

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

TRIM54-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Feb 22, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.43

CADD

Benign

7.9

DANN

Benign

0.84

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