rs6996265

Variant names:

• chr8-66174115-G-A
• rs6996265
• NM_184085.2:c.1525-356G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_184085.2(TRIM55):​c.1525-356G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.232 in 151,016 control chromosomes in the GnomAD database, including 8,115 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.23 (8115 hom., cov: 32)
• Consequence: TRIM55 NM_184085.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.07
• Publications: 7 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.595 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRIM55	NM_184085.2	c.1525-356G>A		intron_variant	Intron 9 of 9	ENST00000315962.9	NP_908973.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TRIM55	ENST00000315962.9	c.1525-356G>A		intron_variant	Intron 9 of 9	1	NM_184085.2	ENSP00000323913.4

Frequencies

GnomAD3 genomes AF: 0.231 AC: 34904 AN: 150904 Hom.: 8085 Cov.: 32

Gnomad AFR AF: 0.601

Gnomad AMI AF: 0.0626

Gnomad AMR AF: 0.122

Gnomad ASJ AF: 0.0737

Gnomad EAS AF: 0.000580

Gnomad SAS AF: 0.0343

Gnomad FIN AF: 0.0969

Gnomad MID AF: 0.0981

Gnomad NFE AF: 0.0958

Gnomad OTH AF: 0.190

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.232 AC: 34985 AN: 151016 Hom.: 8115 Cov.: 32 AF XY: 0.225 AC XY: 16629 AN XY: 73782

African (AFR) AF: 0.601 AC: 24757 AN: 41176

American (AMR) AF: 0.122 AC: 1844 AN: 15166

Ashkenazi Jewish (ASJ) AF: 0.0737 AC: 255 AN: 3462

East Asian (EAS) AF: 0.000581 AC: 3 AN: 5160

South Asian (SAS) AF: 0.0344 AC: 165 AN: 4802

European-Finnish (FIN) AF: 0.0969 AC: 982 AN: 10134

Middle Eastern (MID) AF: 0.0993 AC: 29 AN: 292

European-Non Finnish (NFE) AF: 0.0958 AC: 6499 AN: 67822

Other (OTH) AF: 0.188 AC: 394 AN: 2092

Alfa AF: 0.186 Hom.: 677

Bravo AF: 0.247

Asia WGS AF: 0.0590 AC: 208 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	3.0
DANN	Benign	0.50
PhyloP100		1.1
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs6996265; hg19: chr8-67086350;