Genetic Variant NM_033034.3:c.-2C>G (chr11-5680179-G-C) – 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.-2C>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.531 in 1,597,482 control chromosomes in the GnomAD database, including 231,342 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.43 ( 16359 hom., cov: 31)

Exomes 𝑓: 0.54 ( 214983 hom. )

Consequence

TRIM5
NM_033034.3 5_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0950

Publications

35 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 (BayesDel_noAF=-0.84).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.567 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRIM5	NM_033034.3 link	c.-2C>G		5_prime_UTR_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.-2C>G		5_prime_UTR_variant	Exon 2 of 8	2	NM_033034.3	ENSP00000369373.3		Q9C035-1

Frequencies

GnomAD3 genomes

AF:

0.435

AC:

66051

AN:

151834

Hom.:

16361

Cov.:

show subpopulations

Gnomad AFR

AF:

0.183

Gnomad AMI

AF:

0.600

Gnomad AMR

AF:

0.451

Gnomad ASJ

AF:

0.545

Gnomad EAS

AF:

0.440

Gnomad SAS

AF:

0.585

Gnomad FIN

AF:

0.524

Gnomad MID

AF:

0.462

Gnomad NFE

AF:

0.551

Gnomad OTH

AF:

0.481

GnomAD2 exomes

AF:

0.509

AC:

120882

AN:

237290

AF XY:

0.522

show subpopulations

Gnomad AFR exome

AF:

0.167

Gnomad AMR exome

AF:

0.484

Gnomad ASJ exome

AF:

0.541

Gnomad EAS exome

AF:

0.443

Gnomad FIN exome

AF:

0.529

Gnomad NFE exome

AF:

0.552

Gnomad OTH exome

AF:

0.521

GnomAD4 exome

AF:

0.541

AC:

782116

AN:

1445528

Hom.:

214983

Cov.:

AF XY:

0.544

AC XY:

390393

AN XY:

717344

show subpopulations

African (AFR)

AF:

0.168

AC:

5578

AN:

33300

American (AMR)

AF:

0.482

AC:

21185

AN:

43912

Ashkenazi Jewish (ASJ)

AF:

0.541

AC:

13379

AN:

24710

East Asian (EAS)

AF:

0.449

AC:

17751

AN:

39572

South Asian (SAS)

AF:

0.591

AC:

49011

AN:

82946

European-Finnish (FIN)

AF:

0.526

AC:

27724

AN:

52664

Middle Eastern (MID)

AF:

0.569

AC:

3233

AN:

5684

European-Non Finnish (NFE)

AF:

0.556

AC:

613460

AN:

1102972

Other (OTH)

AF:

0.515

AC:

30795

AN:

59768

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.466

Heterozygous variant carriers

17340

34680

52021

69361

86701

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

17198

34396

51594

68792

85990

<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:

0.435

AC:

66065

AN:

151954

Hom.:

16359

Cov.:

AF XY:

0.437

AC XY:

32444

AN XY:

74240

show subpopulations

African (AFR)

AF:

0.183

AC:

7571

AN:

41464

American (AMR)

AF:

0.451

AC:

6891

AN:

15268

Ashkenazi Jewish (ASJ)

AF:

0.545

AC:

1890

AN:

3466

East Asian (EAS)

AF:

0.439

AC:

2260

AN:

5146

South Asian (SAS)

AF:

0.585

AC:

2812

AN:

4808

European-Finnish (FIN)

AF:

0.524

AC:

5526

AN:

10550

Middle Eastern (MID)

AF:

0.483

AC:

141

AN:

292

European-Non Finnish (NFE)

AF:

0.551

AC:

37410

AN:

67940

Other (OTH)

AF:

0.482

AC:

1017

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1727

3453

5180

6906

8633

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

616

1232

1848

2464

3080

<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:

0.505

Hom.:

4163

Bravo

AF:

0.418

Asia WGS

AF:

0.457

AC:

1592

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

1.4

(source)

DANN

Benign

0.45

PhyloP100

-0.095

PromoterAI

-0.014

Neutral

(source)

Mutation Taster

=300/0

polymorphism (auto)

(source)

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

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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