8-66170497-T-C

Variant names:

• chr8-66170497-T-C
• rs6999100
• NM_184085.2:c.1525-3974T>C

Variant summary

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

The NM_184085.2(TRIM55):​c.1525-3974T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.332 in 152,060 control chromosomes in the GnomAD database, including 12,942 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 0.33 (12942 hom., cov: 32)
• Consequence: TRIM55 NM_184085.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.774
• Publications: 10 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=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.703 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRIM55	NM_184085.2	c.1525-3974T>C		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.1525-3974T>C		intron_variant	Intron 9 of 9	1	NM_184085.2	ENSP00000323913.4

Frequencies

GnomAD3 genomes AF: 0.332 AC: 50399 AN: 151942 Hom.: 12898 Cov.: 32

Gnomad AFR AF: 0.710

Gnomad AMI AF: 0.0779

Gnomad AMR AF: 0.336

Gnomad ASJ AF: 0.123

Gnomad EAS AF: 0.338

Gnomad SAS AF: 0.186

Gnomad FIN AF: 0.144

Gnomad MID AF: 0.152

Gnomad NFE AF: 0.157

Gnomad OTH AF: 0.280

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

GnomAD4 genome AF: 0.332 AC: 50504 AN: 152060 Hom.: 12942 Cov.: 32 AF XY: 0.329 AC XY: 24499 AN XY: 74372

African (AFR) AF: 0.710 AC: 29412 AN: 41428

American (AMR) AF: 0.336 AC: 5134 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.123 AC: 425 AN: 3466

East Asian (EAS) AF: 0.338 AC: 1744 AN: 5164

South Asian (SAS) AF: 0.185 AC: 891 AN: 4820

European-Finnish (FIN) AF: 0.144 AC: 1529 AN: 10600

Middle Eastern (MID) AF: 0.156 AC: 46 AN: 294

European-Non Finnish (NFE) AF: 0.157 AC: 10647 AN: 67978

Other (OTH) AF: 0.286 AC: 605 AN: 2114

Alfa AF: 0.273 Hom.: 7406

Bravo AF: 0.361

Asia WGS AF: 0.289 AC: 1007 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.67
DANN	Benign	0.70
PhyloP100		-0.77
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: rs6999100; hg19: chr8-67082732;