Variant chr11-5679844-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_033034.3(TRIM5):c.334G>T(p.Val112Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0767 in 1,613,378 control chromosomes in the GnomAD database, including 5,741 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 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 nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.063 ( 415 hom., cov: 31)

Exomes 𝑓: 0.078 ( 5326 hom. )

Consequence

TRIM5
NM_033034.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -4.54

Variant links:

Genes affected

TRIM5 (HGNC:16276): (tripartite motif containing 5) The protein encoded by this gene is a member of the tripartite motif (TRIM) family. The TRIM motif includes three zinc-binding domains, a RING, a B-box type 1 and a B-box type 2, and a coiled-coil region. The protein forms homo-oligomers via the coilel-coil region and localizes to cytoplasmic bodies. It appears to function as a E3 ubiquitin-ligase and ubiqutinates itself to regulate its subcellular localization. It may play a role in retroviral restriction. Multiple alternatively spliced transcript variants encoding different isoforms have been described for this gene. [provided by RefSeq, Dec 2009]

TRIM5 links:

TRIM5 (HGNC:):

TRIM5 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0012705624).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.187 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TRIM5	NM_033034.3 linkuse as main transcript	c.334G>T	p.Val112Phe	missense_variant	2/8	ENST00000380034.8	NP_149023.2	Q9C035-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TRIM5	ENST00000380034.8 linkuse as main transcript	c.334G>T	p.Val112Phe	missense_variant	2/8	2	NM_033034.3	ENSP00000369373.3		Q9C035-1

Frequencies

GnomAD3 genomes

AF:

0.0632

AC:

9573

AN:

151434

Hom.:

417

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0156

Gnomad AMI

AF:

0.0549

Gnomad AMR

AF:

0.0759

Gnomad ASJ

AF:

0.0930

Gnomad EAS

AF:

0.0897

Gnomad SAS

AF:

0.198

Gnomad FIN

AF:

0.0798

Gnomad MID

AF:

0.0538

Gnomad NFE

AF:

0.0735

Gnomad OTH

AF:

0.0804

GnomAD3 exomes

AF:

0.0926

AC:

23295

AN:

251454

Hom.:

1430

AF XY:

0.0978

AC XY:

13285

AN XY:

135896

show subpopulations

Gnomad AFR exome

AF:

0.0129

Gnomad AMR exome

AF:

0.108

Gnomad ASJ exome

AF:

0.0991

Gnomad EAS exome

AF:

0.0861

Gnomad SAS exome

AF:

0.186

Gnomad FIN exome

AF:

0.0808

Gnomad NFE exome

AF:

0.0769

Gnomad OTH exome

AF:

0.0915

GnomAD4 exome

AF:

0.0781

AC:

114192

AN:

1461826

Hom.:

5326

Cov.:

AF XY:

0.0817

AC XY:

59437

AN XY:

727216

show subpopulations

Gnomad4 AFR exome

AF:

0.0118

Gnomad4 AMR exome

AF:

0.105

Gnomad4 ASJ exome

AF:

0.0964

Gnomad4 EAS exome

AF:

0.0696

Gnomad4 SAS exome

AF:

0.183

Gnomad4 FIN exome

AF:

0.0798

Gnomad4 NFE exome

AF:

0.0703

Gnomad4 OTH exome

AF:

0.0824

GnomAD4 genome

AF:

0.0631

AC:

9561

AN:

151552

Hom.:

415

Cov.:

AF XY:

0.0665

AC XY:

4920

AN XY:

73972

show subpopulations

Gnomad4 AFR

AF:

0.0155

Gnomad4 AMR

AF:

0.0756

Gnomad4 ASJ

AF:

0.0930

Gnomad4 EAS

AF:

0.0901

Gnomad4 SAS

AF:

0.197

Gnomad4 FIN

AF:

0.0798

Gnomad4 NFE

AF:

0.0735

Gnomad4 OTH

AF:

0.0791

Alfa

AF:

0.0745

Hom.:

588

Bravo

AF:

0.0594

TwinsUK

AF:

0.0680

AC:

252

ALSPAC

AF:

0.0706

AC:

272

ESP6500AA

AF:

0.0164

AC:

ESP6500EA

AF:

0.0796

AC:

684

ExAC

AF:

0.0933

AC:

11325

Asia WGS

AF:

0.124

AC:

432

AN:

3478

EpiCase

AF:

0.0801

EpiControl

AF:

0.0786

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.21

BayesDel_addAF

Benign

-0.58

BayesDel_noAF

Benign

-0.46

CADD

Benign

6.4

DANN

Uncertain

0.98

DEOGEN2

Benign

0.034

T;.;.;.

Eigen

Benign

-1.0

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.037

LIST_S2

Uncertain

0.87

D;D;D;D

MetaRNN

Benign

0.0013

T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.7

L;L;L;.

PrimateAI

Benign

0.32

PROVEAN

Uncertain

-3.3

D;D;D;D

REVEL

Benign

0.11

Sift

Uncertain

0.025

D;D;D;D

Sift4G

Uncertain

0.010

D;D;D;.

Polyphen

0.53

P;B;P;.

Vest4

0.083

MPC

0.17

ClinPred

0.048

GERP RS

-3.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.19

gMVP

0.74

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

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over