Variant 2-27304982-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BS1BS2

The NM_187841.3(TRIM54):c.537G>A(p.Ala179Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00218 in 1,614,090 control chromosomes in the GnomAD database, including 66 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.012 ( 34 hom., cov: 31)

Exomes 𝑓: 0.0012 ( 32 hom. )

Consequence

TRIM54
NM_187841.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -1.55

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 Benign. Variant got -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.4).

BP6

Variant 2-27304982-G-A is Benign according to our data. Variant chr2-27304982-G-A is described in ClinVar as [Benign]. Clinvar id is 775706.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-1.55 with no splicing effect.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0118 (1800/152310) while in subpopulation AFR AF= 0.0413 (1715/41560). AF 95% confidence interval is 0.0396. There are 34 homozygotes in gnomad4. There are 888 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 34 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRIM54	NM_187841.3 link	c.537G>A	p.Ala179Ala	synonymous_variant	Exon 4 of 9	ENST00000380075.7	NP_912730.2	Q9BYV2-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
TRIM54	ENST00000380075.7 link	c.537G>A	p.Ala179Ala	synonymous_variant	Exon 4 of 9	1	NM_187841.3	ENSP00000369415.3	Q9BYV2-1
TRIM54	ENST00000296098.4 link	c.663G>A	p.Ala221Ala	synonymous_variant	Exon 5 of 10	1		ENSP00000296098.4	Q9BYV2-2
TRIM54	ENST00000488321.1 link	n.292G>A		non_coding_transcript_exon_variant	Exon 1 of 2	2

Frequencies

GnomAD3 genomes

AF:

0.0118

AC:

1798

AN:

152192

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0413

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00353

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000206

Gnomad OTH

AF:

0.00813

GnomAD3 exomes

AF:

0.00304

AC:

763

AN:

250782

Hom.:

AF XY:

0.00222

AC XY:

301

AN XY:

135666

show subpopulations

Gnomad AFR exome

AF:

0.0421

Gnomad AMR exome

AF:

0.00159

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000981

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000124

Gnomad OTH exome

AF:

0.00164

GnomAD4 exome

AF:

0.00117

AC:

1711

AN:

1461780

Hom.:

Cov.:

AF XY:

0.00100

AC XY:

729

AN XY:

727188

show subpopulations

Gnomad4 AFR exome

AF:

0.0431

Gnomad4 AMR exome

AF:

0.00201

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000104

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000234

Gnomad4 OTH exome

AF:

0.00230

GnomAD4 genome

AF:

0.0118

AC:

1800

AN:

152310

Hom.:

Cov.:

AF XY:

0.0119

AC XY:

888

AN XY:

74460

show subpopulations

Gnomad4 AFR

AF:

0.0413

Gnomad4 AMR

AF:

0.00353

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000206

Gnomad4 OTH

AF:

0.00804

Alfa

AF:

0.00616

Hom.:

Bravo

AF:

0.0138

Asia WGS

AF:

0.00202

AC:

AN:

3478

EpiCase

AF:

0.0000545

EpiControl

AF:

0.000119

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Mar 29, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

TRIM54-related disorder

Benign:1

Feb 19, 2019

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

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

-0.40

CADD

Benign

1.2

DANN

Benign

0.83

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

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