8-66128397-G-T

Variant names:

• chr8-66128397-G-T
• NM_184085.2:c.262G>T

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_184085.2(TRIM55):​c.262G>T​(p.Asp88Tyr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,552 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: TRIM55 NM_184085.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 9.99

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

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.868

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRIM55	NM_184085.2	c.262G>T	p.Asp88Tyr	missense_variant	Exon 2 of 10	ENST00000315962.9	NP_908973.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TRIM55	ENST00000315962.9	c.262G>T	p.Asp88Tyr	missense_variant	Exon 2 of 10	1	NM_184085.2	ENSP00000323913.4
TRIM55	ENST00000276573.11	c.262G>T	p.Asp88Tyr	missense_variant	Exon 2 of 11	1		ENSP00000276573.7
TRIM55	ENST00000353317.9	c.262G>T	p.Asp88Tyr	missense_variant	Exon 2 of 9	1		ENSP00000297348.8
TRIM55	ENST00000350034.4	c.262G>T	p.Asp88Tyr	missense_variant	Exon 2 of 5	1		ENSP00000332302.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1461552 Hom.: 0 Cov.: 30 AF XY: 0.00000413 AC XY: 3 AN XY: 727064

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000270

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jan 28, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.262G>T (p.D88Y) alteration is located in exon 2 (coding exon 2) of the TRIM55 gene. This alteration results from a G to T substitution at nucleotide position 262, causing the aspartic acid (D) at amino acid position 88 to be replaced by a tyrosine (Y). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.99
BayesDel_addAF	Pathogenic	0.22	D
BayesDel_noAF	Uncertain	0.080
CADD	Pathogenic	33
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.65	.;D;.;.
Eigen	Pathogenic	0.99
Eigen_PC	Pathogenic	0.97
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.97	D;D;D;D
M_CAP	Benign	0.060	D
MetaRNN	Pathogenic	0.87	D;D;D;D
MetaSVM	Benign	-0.79	T
MutationAssessor	Pathogenic	3.1	M;M;M;M
PrimateAI	Pathogenic	0.80	T
PROVEAN	Pathogenic	-8.7	D;D;D;D
REVEL	Uncertain	0.53
Sift	Uncertain	0.0010	D;D;D;D
Sift4G	Pathogenic	0.0010	D;D;D;D
Polyphen		1.0	D;D;D;D
Vest4		0.84
MutPred		0.53		Gain of MoRF binding (P = 0.0802);Gain of MoRF binding (P = 0.0802);Gain of MoRF binding (P = 0.0802);Gain of MoRF binding (P = 0.0802);
MVP		0.69
MPC		0.29
ClinPred		1.0	D
GERP RS		5.8
Varity_R		0.91
gMVP		0.75

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr8-67040632;