dbSNP rs4434604: TRIM55:p.Glu329Glu (chr8-66152378-A-G) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. The variant received -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

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 VariationId 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 rank	MANE	Protein	UniProt
TRIM55	NM_184085.2 link	c.987A>G	p.Glu329Glu	splice_region_variant, synonymous_variant	Exon 8 of 10	ENST00000315962.9	NP_908973.1	Q9BYV6-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TRIM55	ENST00000315962.9 link	c.987A>G	p.Glu329Glu	splice_region_variant, synonymous_variant	Exon 8 of 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

GnomAD2 exomes

AF:

0.0133

AC:

2655

AN:

199684

AF XY:

0.0117

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 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

African (AFR)

AF:

0.000515

AC:

AN:

33024

American (AMR)

AF:

0.0298

AC:

1151

AN:

38668

Ashkenazi Jewish (ASJ)

AF:

0.00130

AC:

AN:

25432

East Asian (EAS)

AF:

0.0959

AC:

3727

AN:

38862

South Asian (SAS)

AF:

0.00341

AC:

283

AN:

82872

European-Finnish (FIN)

AF:

0.0000203

AC:

AN:

49330

Middle Eastern (MID)

AF:

0.000532

AC:

AN:

5636

European-Non Finnish (NFE)

AF:

0.0000822

AC:

AN:

1095386

Other (OTH)

AF:

0.00661

AC:

392

AN:

59268

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

357

714

1072

1429

1786

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

164

246

328

410

<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

AF:

0.00640

AC:

975

AN:

152276

Hom.:

Cov.:

AF XY:

0.00736

AC XY:

548

AN XY:

74464

show subpopulations

African (AFR)

AF:

0.000457

AC:

AN:

41546

American (AMR)

AF:

0.0226

AC:

345

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.000864

AC:

AN:

3472

East Asian (EAS)

AF:

0.107

AC:

553

AN:

5178

South Asian (SAS)

AF:

0.00746

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10624

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000294

AC:

AN:

68016

Other (OTH)

AF:

0.00803

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

133

178

222

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00319

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

Sep 24, 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

-0.57

CADD

Benign

(source)

DANN

Benign

0.54

PhyloP100

0.92

Mutation Taster

=77/23

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over