11-55885705-T-C

Position:

• chr11-55885705-T-C

Variant summary

Our verdict is Likely pathogenic. Variant got 8 ACMG points: 8P and 0B. PM1 PM2 PP3_Strong

The NM_032681.4(TRIM51):​c.277T>C​(p.Cys93Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000151 in 1,459,332 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: 0.000015 (0 hom.)
• Consequence: TRIM51 NM_032681.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.56

Genes affected

TRIM51 (HGNC:19023): (tripartite motif-containing 51) Predicted to enable ubiquitin protein ligase activity. Predicted to be involved in innate immune response; protein ubiquitination; and regulation of gene expression. Predicted to be active in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Likely_pathogenic. Variant got 8 ACMG points.

• PM1: In a binding_site (size 0) in uniprot entity TRI51_HUMAN
• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.946

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TRIM51	NM_032681.4	c.277T>C	p.Cys93Arg	missense_variant	2/7	ENST00000449290.6	NP_116070.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TRIM51	ENST00000449290.6	c.277T>C	p.Cys93Arg	missense_variant	2/7	5	NM_032681.4	ENSP00000395086	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.0000151 AC: 22 AN: 1459332 Hom.: 0 Cov.: 33 AF XY: 0.00000551 AC XY: 4 AN XY: 725954

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: 0.0000189

Gnomad4 OTH exome AF: 0.0000166

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 26, 2022

The c.277T>C (p.C93R) alteration is located in exon 2 (coding exon 1) of the TRIM51 gene. This alteration results from a T to C substitution at nucleotide position 277, causing the cysteine (C) at amino acid position 93 to be replaced by an arginine (R). 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	Uncertain	0.48
BayesDel_addAF	Uncertain	0.15	D
BayesDel_noAF	Uncertain	-0.030
CADD	Benign	18
DANN	Benign	0.95
DEOGEN2	Benign	0.39	T
Eigen	Benign	0.014
Eigen_PC	Benign	-0.38
FATHMM_MKL	Benign	0.020	N
LIST_S2	Benign	0.83	T
M_CAP	Benign	0.0071	T
MetaRNN	Pathogenic	0.95	D
MetaSVM	Pathogenic	0.89	D
MutationAssessor	Pathogenic	4.4	H
MutationTaster	Benign	1.0	N
PrimateAI	Uncertain	0.58	T
PROVEAN	Pathogenic	-9.8	D
REVEL	Uncertain	0.34
Sift	Pathogenic	0.0	D
Sift4G	Uncertain	0.0020	D
Polyphen		1.0	D
Vest4		0.46
MutPred		0.91		Gain of MoRF binding (P = 0.0234);
MVP		0.85
MPC		0.59
ClinPred		1.0	D
GERP RS		0.80
Varity_R		0.58
gMVP		0.32

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr11-55653181; COSMIC: COSV99792896; COSMIC: COSV99792896;