8-66137119-A-T

Variant names:

• chr8-66137119-A-T
• rs763298747
• NM_184085.2:c.532A>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.532A>T​(p.Ile178Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000103 in 1,461,826 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. 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. I178V) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.000010 (0 hom.)
• Consequence: TRIM55 NM_184085.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.02
• Publications: 0 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=0.12455627).

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.532A>T	p.Ile178Phe	missense	Exon 4 of 10	NP_908973.1	Q9BYV6-1
	TRIM55	NM_033058.3		c.532A>T	p.Ile178Phe	missense	Exon 4 of 11	NP_149047.2
	TRIM55	NM_184086.2		c.532A>T	p.Ile178Phe	missense	Exon 4 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.532A>T	p.Ile178Phe	missense	Exon 4 of 10	ENSP00000323913.4	Q9BYV6-1
	TRIM55	ENST00000276573.11	TSL:1	c.532A>T	p.Ile178Phe	missense	Exon 4 of 11	ENSP00000276573.7	Q9BYV6-3
	TRIM55	ENST00000353317.9	TSL:1	c.532A>T	p.Ile178Phe	missense	Exon 4 of 9	ENSP00000297348.8	Q9BYV6-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.0000103 AC: 15 AN: 1461826 Hom.: 0 Cov.: 30 AF XY: 0.00000688 AC XY: 5 AN XY: 727206

African (AFR) AF: 0.000239 AC: 8 AN: 33478

American (AMR) AF: 0.00 AC: 0 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26132

East Asian (EAS) AF: 0.00 AC: 0 AN: 39696

South Asian (SAS) AF: 0.00 AC: 0 AN: 86254

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53414

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5760

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111976

Other (OTH) AF: 0.000116 AC: 7 AN: 60394

GnomAD4 genome Cov.: 32

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.61
CADD	Benign	16
DANN	Benign	0.88
DEOGEN2	Benign	0.26	T
Eigen	Benign	-0.59
Eigen_PC	Benign	-0.51
FATHMM_MKL	Uncertain	0.84	D
LIST_S2	Uncertain	0.95	D
M_CAP	Benign	0.018	T
MetaRNN	Benign	0.12	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.4	L
PhyloP100		2.0
PrimateAI	Benign	0.36	T
PROVEAN	Benign	-1.8	N
REVEL	Benign	0.027
Sift	Uncertain	0.013	D
Sift4G	Benign	0.25	T
Polyphen		0.071	B
Vest4		0.42
MutPred		0.41		Loss of stability (P = 0.0648)
MVP		0.18
MPC		0.054
ClinPred		0.53	D
GERP RS		2.5
Varity_R		0.073
gMVP		0.36
Mutation Taster		=86/14	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs763298747; hg19: chr8-67049354;