Variant rs4434604 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BA1

The NM_184085.2(TRIM55):c.987A>G(p.Glu329Glu) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00422 in 1,580,754 control chromosomes in the GnomAD database, including 217 homozygotes. In-silico tool predicts a benign outcome for this variant. 2/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.0064 ( 39 hom., cov: 32)

Exomes 𝑓: 0.0040 ( 178 hom. )

Consequence

TRIM55
NM_184085.2 splice_region, synonymous

Scores

Splicing: ADA: 0.00003126

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 0.922

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 Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.57).

BP6

Variant 8-66152378-A-G is Benign according to our data. Variant chr8-66152378-A-G is described in ClinVar as [Benign]. Clinvar id is 3060835.Status of the report is no_assertion_criteria_provided, 0 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0994 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TRIM55	NM_184085.2 link	c.987A>G	p.Glu329Glu	splice_region_variant, synonymous_variant	8/10	ENST00000315962.9	NP_908973.1	Q9BYV6-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TRIM55	ENST00000315962.9 link	c.987A>G	p.Glu329Glu	splice_region_variant, synonymous_variant	8/10	1	NM_184085.2	ENSP00000323913.4		Q9BYV6-1

Frequencies

GnomAD3 genomes

AF:

0.00640

AC:

974

AN:

152158

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000459

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0223

Gnomad ASJ

AF:

0.000864

Gnomad EAS

AF:

0.107

Gnomad SAS

AF:

0.00745

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00812

GnomAD3 exomes

AF:

0.0133

AC:

2655

AN:

199684

Hom.:

AF XY:

0.0117

AC XY:

1248

AN XY:

106990

show subpopulations

Gnomad AFR exome

AF:

0.000481

Gnomad AMR exome

AF:

0.0311

Gnomad ASJ exome

AF:

0.00166

Gnomad EAS exome

AF:

0.109

Gnomad SAS exome

AF:

0.00311

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000812

Gnomad OTH exome

AF:

0.00612

GnomAD4 exome

AF:

0.00399

AC:

5697

AN:

1428478

Hom.:

178

Cov.:

AF XY:

0.00384

AC XY:

2720

AN XY:

707708

show subpopulations

Gnomad4 AFR exome

AF:

0.000515

Gnomad4 AMR exome

AF:

0.0298

Gnomad4 ASJ exome

AF:

0.00130

Gnomad4 EAS exome

AF:

0.0959

Gnomad4 SAS exome

AF:

0.00341

Gnomad4 FIN exome

AF:

0.0000203

Gnomad4 NFE exome

AF:

0.0000822

Gnomad4 OTH exome

AF:

0.00661

GnomAD4 genome

AF:

0.00640

AC:

975

AN:

152276

Hom.:

Cov.:

AF XY:

0.00736

AC XY:

548

AN XY:

74464

show subpopulations

Gnomad4 AFR

AF:

0.000457

Gnomad4 AMR

AF:

0.0226

Gnomad4 ASJ

AF:

0.000864

Gnomad4 EAS

AF:

0.107

Gnomad4 SAS

AF:

0.00746

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.00803

Alfa

AF:

0.00302

Hom.:

Bravo

AF:

0.00894

Asia WGS

AF:

0.0380

AC:

133

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

TRIM55-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Sep 24, 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

-0.57

CADD

Benign

DANN

Benign

0.54

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000031

dbscSNV1_RF

Benign

0.0080

SpliceAI score (max)

0.47

Details are displayed if max score is > 0.2

DS_AG_spliceai

0.47

Position offset: 1

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