Variant 11-5667710-C-T 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.746G>A(p.Gly249Asp) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0917 in 1,611,612 control chromosomes in the GnomAD database, including 12,698 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. 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 0.14 ( 2459 hom., cov: 32)

Exomes 𝑓: 0.086 ( 10239 hom. )

Consequence

TRIM5
NM_033034.3 missense, splice_region

Scores

Splicing: ADA: 0.00001234

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.145

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:

(HGNC:):

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=0.0012489855).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.416 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TRIM5	NM_033034.3 linkuse as main transcript	c.746G>A	p.Gly249Asp	missense_variant, splice_region_variant	5/8	ENST00000380034.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TRIM5	ENST00000380034.8 linkuse as main transcript	c.746G>A	p.Gly249Asp	missense_variant, splice_region_variant	5/8	2	NM_033034.3	P1	Q9C035-1

Frequencies

GnomAD3 genomes

AF:

0.144

AC:

21868

AN:

151932

Hom.:

2457

Cov.:

show subpopulations

Gnomad AFR

AF:

0.254

Gnomad AMI

AF:

0.0417

Gnomad AMR

AF:

0.214

Gnomad ASJ

AF:

0.0543

Gnomad EAS

AF:

0.430

Gnomad SAS

AF:

0.164

Gnomad FIN

AF:

0.0590

Gnomad MID

AF:

0.0918

Gnomad NFE

AF:

0.0577

Gnomad OTH

AF:

0.132

GnomAD3 exomes

AF:

0.143

AC:

35854

AN:

250190

Hom.:

4608

AF XY:

0.133

AC XY:

18025

AN XY:

135314

show subpopulations

Gnomad AFR exome

AF:

0.265

Gnomad AMR exome

AF:

0.289

Gnomad ASJ exome

AF:

0.0494

Gnomad EAS exome

AF:

0.444

Gnomad SAS exome

AF:

0.151

Gnomad FIN exome

AF:

0.0590

Gnomad NFE exome

AF:

0.0579

Gnomad OTH exome

AF:

0.115

GnomAD4 exome

AF:

0.0862

AC:

125813

AN:

1459562

Hom.:

10239

Cov.:

AF XY:

0.0864

AC XY:

62707

AN XY:

726164

show subpopulations

Gnomad4 AFR exome

AF:

0.262

Gnomad4 AMR exome

AF:

0.278

Gnomad4 ASJ exome

AF:

0.0531

Gnomad4 EAS exome

AF:

0.421

Gnomad4 SAS exome

AF:

0.148

Gnomad4 FIN exome

AF:

0.0588

Gnomad4 NFE exome

AF:

0.0573

Gnomad4 OTH exome

AF:

0.111

GnomAD4 genome

AF:

0.144

AC:

21905

AN:

152050

Hom.:

2459

Cov.:

AF XY:

0.147

AC XY:

10966

AN XY:

74346

show subpopulations

Gnomad4 AFR

AF:

0.254

Gnomad4 AMR

AF:

0.214

Gnomad4 ASJ

AF:

0.0543

Gnomad4 EAS

AF:

0.431

Gnomad4 SAS

AF:

0.164

Gnomad4 FIN

AF:

0.0590

Gnomad4 NFE

AF:

0.0578

Gnomad4 OTH

AF:

0.133

Alfa

AF:

0.0830

Hom.:

2497

Bravo

AF:

0.166

TwinsUK

AF:

0.0499

AC:

185

ALSPAC

AF:

0.0623

AC:

240

ESP6500AA

AF:

0.255

AC:

1122

ESP6500EA

AF:

0.0584

AC:

502

ExAC

AF:

0.141

AC:

17136

Asia WGS

AF:

0.300

AC:

1040

AN:

3478

EpiCase

AF:

0.0570

EpiControl

AF:

0.0570

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.088

BayesDel_addAF

Benign

-0.63

BayesDel_noAF

Benign

-0.54

CADD

Benign

3.8

DANN

Benign

0.086

DEOGEN2

Benign

0.00012

T;.;.

Eigen

Benign

-0.44

Eigen_PC

Benign

-0.52

FATHMM_MKL

Benign

0.0030

LIST_S2

Benign

0.58

T;T;T

MetaRNN

Benign

0.0012

T;T;T

MetaSVM

Benign

-0.91

MutationAssessor

Benign

0.61

N;N;N

MutationTaster

Benign

0.98

P;P;P;P;P;P

PrimateAI

Benign

0.26

PROVEAN

Benign

4.0

N;N;N

REVEL

Benign

0.12

Sift

Benign

1.0

T;T;T

Sift4G

Benign

1.0

T;T;T

Polyphen

0.0

B;B;B

Vest4

0.040

MPC

0.064

ClinPred

0.00059

GERP RS

1.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.062

gMVP

0.15

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000012

dbscSNV1_RF

Benign

0.0020

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over