Genetic Variant NM_033034.3:c.334G>T (chr11-5679844-C-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -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. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

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

Publications

67 publications found

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
TRIM5	NM_033034.3 link	c.334G>T	p.Val112Phe	missense_variant	Exon 2 of 8	ENST00000380034.8	NP_149023.2	Q9C035-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TRIM5	ENST00000380034.8 link	c.334G>T	p.Val112Phe	missense_variant	Exon 2 of 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

GnomAD2 exomes

AF:

0.0926

AC:

23295

AN:

251454

AF XY:

0.0978

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 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

African (AFR)

AF:

0.0118

AC:

394

AN:

33480

American (AMR)

AF:

0.105

AC:

4693

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.0964

AC:

2520

AN:

26134

East Asian (EAS)

AF:

0.0696

AC:

2764

AN:

39700

South Asian (SAS)

AF:

0.183

AC:

15797

AN:

86254

European-Finnish (FIN)

AF:

0.0798

AC:

4265

AN:

53420

Middle Eastern (MID)

AF:

0.0978

AC:

564

AN:

5768

European-Non Finnish (NFE)

AF:

0.0703

AC:

78219

AN:

1111954

Other (OTH)

AF:

0.0824

AC:

4976

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.474

Heterozygous variant carriers

6453

12906

19360

25813

32266

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2944

5888

8832

11776

14720

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0631

AC:

9561

AN:

151552

Hom.:

415

Cov.:

AF XY:

0.0665

AC XY:

4920

AN XY:

73972

show subpopulations

African (AFR)

AF:

0.0155

AC:

642

AN:

41364

American (AMR)

AF:

0.0756

AC:

1150

AN:

15204

Ashkenazi Jewish (ASJ)

AF:

0.0930

AC:

322

AN:

3464

East Asian (EAS)

AF:

0.0901

AC:

458

AN:

5084

South Asian (SAS)

AF:

0.197

AC:

929

AN:

4712

European-Finnish (FIN)

AF:

0.0798

AC:

839

AN:

10508

Middle Eastern (MID)

AF:

0.0510

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0735

AC:

4991

AN:

67926

Other (OTH)

AF:

0.0791

AC:

165

AN:

2086

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

446

891

1337

1782

2228

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

122

244

366

488

610

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0705

Hom.:

812

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

(source)

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;.

PhyloP100

-4.5

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

PromoterAI

0.021

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.19

gMVP

0.74

Mutation Taster

=99/1

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over