8-66135039-C-T

Variant names:

• chr8-66135039-C-T
• rs150193661
• NM_184085.2:c.391C>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_184085.2(TRIM55):​c.391C>T​(p.Arg131Cys) variant causes a missense change. The variant allele was found at a frequency of 0.000113 in 1,614,158 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R131H) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.00032 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000092 (1 hom.)
• Consequence: TRIM55 NM_184085.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.42
• 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: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.22228256).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRIM55	NM_184085.2	MANE Select	c.391C>T	p.Arg131Cys	missense	Exon 3 of 10	NP_908973.1	Q9BYV6-1
	TRIM55	NM_033058.3		c.391C>T	p.Arg131Cys	missense	Exon 3 of 11	NP_149047.2
	TRIM55	NM_184086.2		c.391C>T	p.Arg131Cys	missense	Exon 3 of 9	NP_908974.1	Q9BYV6-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRIM55	ENST00000315962.9	TSL:1 MANE Select	c.391C>T	p.Arg131Cys	missense	Exon 3 of 10	ENSP00000323913.4	Q9BYV6-1
	TRIM55	ENST00000276573.11	TSL:1	c.391C>T	p.Arg131Cys	missense	Exon 3 of 11	ENSP00000276573.7	Q9BYV6-3
	TRIM55	ENST00000353317.9	TSL:1	c.391C>T	p.Arg131Cys	missense	Exon 3 of 9	ENSP00000297348.8	Q9BYV6-2

Frequencies

GnomAD3 genomes AF: 0.000315 AC: 48 AN: 152168 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000941

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000196

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000441

Gnomad OTH AF: 0.00144

GnomAD2 exomes AF: 0.000131 AC: 33 AN: 251434 AF XY: 0.0000957

Gnomad AFR exome AF: 0.000861

Gnomad AMR exome AF: 0.000145

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000791

Gnomad OTH exome AF: 0.000815

GnomAD4 exome AF: 0.0000917 AC: 134 AN: 1461872 Hom.: 1 Cov.: 32 AF XY: 0.0000935 AC XY: 68 AN XY: 727238

African (AFR) AF: 0.00119 AC: 40 AN: 33480

American (AMR) AF: 0.000179 AC: 8 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00104 AC: 6 AN: 5768

European-Non Finnish (NFE) AF: 0.0000558 AC: 62 AN: 1111994

Other (OTH) AF: 0.000298 AC: 18 AN: 60396

GnomAD4 genome AF: 0.000315 AC: 48 AN: 152286 Hom.: 0 Cov.: 32 AF XY: 0.000215 AC XY: 16 AN XY: 74460

African (AFR) AF: 0.000939 AC: 39 AN: 41552

American (AMR) AF: 0.000196 AC: 3 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10606

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

European-Non Finnish (NFE) AF: 0.0000441 AC: 3 AN: 68032

Other (OTH) AF: 0.00142 AC: 3 AN: 2112

Alfa AF: 0.000366 Hom.: 0

Bravo AF: 0.000366

ESP6500AA AF: 0.000454 AC: 2

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.000140 AC: 17

EpiCase AF: 0.00

EpiControl AF: 0.000237

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.24
BayesDel_addAF	Benign	-0.31	T
BayesDel_noAF	Benign	-0.27
CADD	Pathogenic	32
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.35	T
Eigen	Pathogenic	0.76
Eigen_PC	Pathogenic	0.73
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Pathogenic	0.98	D
M_CAP	Benign	0.035	D
MetaRNN	Benign	0.22	T
MetaSVM	Benign	-0.62	T
MutationAssessor	Uncertain	2.6	M
PhyloP100		5.4
PrimateAI	Uncertain	0.56	T
PROVEAN	Pathogenic	-5.3	D
REVEL	Benign	0.28
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0010	D
Polyphen		1.0	D
Vest4		0.69
MVP		0.76
MPC		0.28
ClinPred		0.21	T
GERP RS		4.6
Varity_R		0.62
gMVP		0.54
Mutation Taster		=80/20	polymorphism

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: rs150193661; hg19: chr8-67047274; COSMIC: COSV52545301;