chr8-66152378-A-G

Variant names:

• chr8-66152378-A-G
• rs4434604
• NM_184085.2:c.987A>G

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP6 BA1

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

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]

ACMG classification

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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_184085.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRIM55	NM_184085.2	MANE Select	c.987A>G	p.Glu329Glu	splice_region synonymous	Exon 8 of 10	NP_908973.1
	TRIM55	NM_033058.3		c.987A>G	p.Glu329Glu	splice_region synonymous	Exon 8 of 11	NP_149047.2
	TRIM55	NM_184086.2		c.987A>G	p.Glu329Glu	splice_region synonymous	Exon 8 of 9	NP_908974.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRIM55	ENST00000315962.9	TSL:1 MANE Select	c.987A>G	p.Glu329Glu	splice_region synonymous	Exon 8 of 10	ENSP00000323913.4
	TRIM55	ENST00000276573.11	TSL:1	c.987A>G	p.Glu329Glu	splice_region synonymous	Exon 8 of 11	ENSP00000276573.7
	TRIM55	ENST00000353317.9	TSL:1	c.987A>G	p.Glu329Glu	splice_region synonymous	Exon 8 of 9	ENSP00000297348.8

Frequencies

GnomAD3 genomes AF: 0.00640 AC: 974 AN: 152158 Hom.: 37 Cov.: 32

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

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.: 30 AF XY: 0.00384 AC XY: 2720 AN XY: 707708

African (AFR) AF: 0.000515 AC: 17 AN: 33024

American (AMR) AF: 0.0298 AC: 1151 AN: 38668

Ashkenazi Jewish (ASJ) AF: 0.00130 AC: 33 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: 1 AN: 49330

Middle Eastern (MID) AF: 0.000532 AC: 3 AN: 5636

European-Non Finnish (NFE) AF: 0.0000822 AC: 90 AN: 1095386

Other (OTH) AF: 0.00661 AC: 392 AN: 59268

GnomAD4 genome AF: 0.00640 AC: 975 AN: 152276 Hom.: 39 Cov.: 32 AF XY: 0.00736 AC XY: 548 AN XY: 74464

African (AFR) AF: 0.000457 AC: 19 AN: 41546

American (AMR) AF: 0.0226 AC: 345 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.000864 AC: 3 AN: 3472

East Asian (EAS) AF: 0.107 AC: 553 AN: 5178

South Asian (SAS) AF: 0.00746 AC: 36 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 68016

Other (OTH) AF: 0.00803 AC: 17 AN: 2116

Alfa AF: 0.00319 Hom.: 37

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

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.57
CADD	Benign	17
DANN	Benign	0.54
PhyloP100		0.92
Mutation Taster		=77/23	polymorphism (auto)

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

Other links and lift over

dbSNP: rs4434604; hg19: chr8-67064613; COSMIC: COSV52544644;