Variant 11-55888052-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_032681.4(TRIM51):c.528A>G(p.Ile176Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000793 in 1,607,780 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00047 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00083 ( 0 hom. )

Consequence

TRIM51
NM_032681.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.122

Variant links:

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]

TRIM51 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.014266193).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TRIM51	NM_032681.4 linkuse as main transcript	c.528A>G	p.Ile176Met	missense_variant	4/7	ENST00000449290.6	NP_116070.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TRIM51	ENST00000449290.6 linkuse as main transcript	c.528A>G	p.Ile176Met	missense_variant	4/7	5	NM_032681.4	ENSP00000395086	P1	Q9BSJ1-1
TRIM51	ENST00000244891.3 linkuse as main transcript	c.99A>G	p.Ile33Met	missense_variant	2/5	1		ENSP00000244891		Q9BSJ1-2

Frequencies

GnomAD3 genomes

AF:

0.000466

AC:

AN:

152202

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000217

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000196

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000188

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000823

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000515

AC:

128

AN:

248392

Hom.:

AF XY:

0.000571

AC XY:

AN XY:

134798

show subpopulations

Gnomad AFR exome

AF:

0.000197

Gnomad AMR exome

AF:

0.000174

Gnomad ASJ exome

AF:

0.000698

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000232

Gnomad NFE exome

AF:

0.000935

Gnomad OTH exome

AF:

0.000333

GnomAD4 exome

AF:

0.000827

AC:

1204

AN:

1455460

Hom.:

Cov.:

AF XY:

0.000799

AC XY:

579

AN XY:

724570

show subpopulations

Gnomad4 AFR exome

AF:

0.000120

Gnomad4 AMR exome

AF:

0.000202

Gnomad4 ASJ exome

AF:

0.00123

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.000281

Gnomad4 NFE exome

AF:

0.00100

Gnomad4 OTH exome

AF:

0.000565

GnomAD4 genome

AF:

0.000466

AC:

AN:

152320

Hom.:

Cov.:

AF XY:

0.000430

AC XY:

AN XY:

74484

show subpopulations

Gnomad4 AFR

AF:

0.000216

Gnomad4 AMR

AF:

0.000196

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000188

Gnomad4 NFE

AF:

0.000823

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000647

Hom.:

Bravo

AF:

0.000465

ESP6500AA

AF:

0.000455

AC:

ESP6500EA

AF:

0.000700

AC:

ExAC

AF:

0.000420

AC:

EpiCase

AF:

0.000982

EpiControl

AF:

0.00113

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 22, 2021

The c.528A>G (p.I176M) alteration is located in exon 4 (coding exon 3) of the TRIM51 gene. This alteration results from a A to G substitution at nucleotide position 528, causing the isoleucine (I) at amino acid position 176 to be replaced by a methionine (M). 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

Benign

0.068

BayesDel_addAF

Benign

-0.66

BayesDel_noAF

Benign

-0.78

CADD

Benign

2.3

DANN

Benign

0.20

DEOGEN2

Benign

0.0040

T;.

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.00034

LIST_S2

Benign

0.048

T;T

M_CAP

Benign

0.0015

MetaRNN

Benign

0.014

T;T

MetaSVM

Benign

-0.94

MutationAssessor

Benign

1.1

L;.

MutationTaster

Benign

1.0

N;N

PrimateAI

Uncertain

0.54

PROVEAN

Benign

0.80

N;N

REVEL

Benign

0.016

Sift

Benign

0.091

T;T

Sift4G

Uncertain

0.051

T;T

Polyphen

0.0020

B;.

Vest4

0.13

MVP

0.076

MPC

0.080

ClinPred

0.0057

Varity_R

0.16

gMVP

0.12

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over