chr8-66135141-T-G

Variant names:

• chr8-66135141-T-G
• rs748783640
• NM_184085.2:c.493T>G

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_184085.2(TRIM55):​c.493T>G​(p.Phe165Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. F165L) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: TRIM55 NM_184085.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.99
• Publications: 1 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: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.493T>G	p.Phe165Val	missense	Exon 3 of 10	NP_908973.1	Q9BYV6-1
	TRIM55	NM_033058.3		c.493T>G	p.Phe165Val	missense	Exon 3 of 11	NP_149047.2
	TRIM55	NM_184086.2		c.493T>G	p.Phe165Val	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.493T>G	p.Phe165Val	missense	Exon 3 of 10	ENSP00000323913.4	Q9BYV6-1
	TRIM55	ENST00000276573.11	TSL:1	c.493T>G	p.Phe165Val	missense	Exon 3 of 11	ENSP00000276573.7	Q9BYV6-3
	TRIM55	ENST00000353317.9	TSL:1	c.493T>G	p.Phe165Val	missense	Exon 3 of 9	ENSP00000297348.8	Q9BYV6-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.78
BayesDel_addAF	Uncertain	0.025	T
BayesDel_noAF	Benign	-0.20
CADD	Pathogenic	30
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.63	D
Eigen	Uncertain	0.47
Eigen_PC	Uncertain	0.57
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.94	D
M_CAP	Benign	0.046	D
MetaRNN	Uncertain	0.47	T
MetaSVM	Benign	-0.75	T
MutationAssessor	Benign	1.4	L
PhyloP100		8.0
PrimateAI	Uncertain	0.77	T
PROVEAN	Pathogenic	-5.2	D
REVEL	Uncertain	0.30
Sift	Uncertain	0.0020	D
Sift4G	Uncertain	0.027	D
Polyphen		0.71	P
Vest4		0.53
MutPred		0.61		Loss of catalytic residue at F165 (P = 0.0077)
MVP		0.55
MPC		0.28
ClinPred		1.0	D
GERP RS		5.8
Varity_R		0.84
gMVP		0.56
Mutation Taster		=42/58	disease causing

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: rs748783640; hg19: chr8-67047376;