8-66175587-A-G

Variant names:

• chr8-66175587-A-G
• rs11986876
• NM_184085.2:c.*994A>G

Variant summary

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

The NM_184085.2(TRIM55):​c.*994A>G variant causes a downstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0237 in 152,302 control chromosomes in the GnomAD database, including 142 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 0.024 (142 hom., cov: 32)
  • Failed GnomAD Quality Control
• Consequence: TRIM55 NM_184085.2 downstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0400
• 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0748 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRIM55	NM_184085.2	c.*994A>G		downstream_gene_variant		ENST00000315962.9	NP_908973.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TRIM55	ENST00000315962.9	c.*994A>G		downstream_gene_variant		1	NM_184085.2	ENSP00000323913.4
TRIM55	ENST00000353317.9	c.*994A>G		downstream_gene_variant		1		ENSP00000297348.8

Frequencies

GnomAD3 genomes AF: 0.0236 AC: 3584 AN: 152182 Hom.: 139 Cov.: 32

Gnomad AFR AF: 0.0767

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0137

Gnomad ASJ AF: 0.0167

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000828

Gnomad FIN AF: 0.0000942

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.00131

Gnomad OTH AF: 0.0191

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

GnomAD4 genome AF: 0.0237 AC: 3607 AN: 152302 Hom.: 142 Cov.: 32 AF XY: 0.0231 AC XY: 1724 AN XY: 74482

African (AFR) AF: 0.0770 AC: 3200 AN: 41556

American (AMR) AF: 0.0137 AC: 209 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.0167 AC: 58 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5190

South Asian (SAS) AF: 0.000829 AC: 4 AN: 4826

European-Finnish (FIN) AF: 0.0000942 AC: 1 AN: 10620

Middle Eastern (MID) AF: 0.0204 AC: 6 AN: 294

European-Non Finnish (NFE) AF: 0.00131 AC: 89 AN: 68018

Other (OTH) AF: 0.0189 AC: 40 AN: 2112

Alfa AF: 0.0132 Hom.: 20

Bravo AF: 0.0272

Asia WGS AF: 0.00435 AC: 16 AN: 3462

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	11
DANN	Benign	0.72
PhyloP100		0.040

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs11986876; hg19: chr8-67087822;