dbSNP rs28381981: TRIM5:p.His419Tyr (chr11-5665036-G-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.1255C>T(p.His419Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0581 in 1,614,040 control chromosomes in the GnomAD database, including 3,148 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 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 0.042 ( 214 hom., cov: 32)

Exomes 𝑓: 0.060 ( 2934 hom. )

Consequence

TRIM5
NM_033034.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.846

Publications

26 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:

ENSG00000239920 (HGNC:):

ENSG00000239920 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=0.0032238066).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0628 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_033034.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TRIM5	NM_033034.3	MANE Select	c.1255C>T	p.His419Tyr	missense	Exon 8 of 8	NP_149023.2	Q9C035-1
TRIM5	NM_033092.4		c.*471C>T		3_prime_UTR	Exon 7 of 7	NP_149083.2	Q9C035-3
TRIM5	NM_001410958.1		c.*356C>T		3_prime_UTR	Exon 7 of 7	NP_001397887.1	A0A804HHS7

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TRIM5	ENST00000380034.8	TSL:2 MANE Select	c.1255C>T	p.His419Tyr	missense	Exon 8 of 8	ENSP00000369373.3	Q9C035-1
TRIM5	ENST00000396847.7	TSL:1	c.*471C>T		3_prime_UTR	Exon 7 of 7	ENSP00000380058.3	Q9C035-3
ENSG00000239920	ENST00000380259.7	TSL:5	n.231+13168C>T		intron	N/A	ENSP00000369609.3	A0A2U3TZJ3

Frequencies

GnomAD3 genomes

AF:

0.0416

AC:

6320

AN:

152078

Hom.:

214

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0112

Gnomad AMI

AF:

0.151

Gnomad AMR

AF:

0.0309

Gnomad ASJ

AF:

0.0631

Gnomad EAS

AF:

0.00135

Gnomad SAS

AF:

0.0600

Gnomad FIN

AF:

0.0231

Gnomad MID

AF:

0.0475

Gnomad NFE

AF:

0.0644

Gnomad OTH

AF:

0.0465

GnomAD2 exomes

AF:

0.0465

AC:

11679

AN:

251370

AF XY:

0.0494

show subpopulations

Gnomad AFR exome

AF:

0.00874

Gnomad AMR exome

AF:

0.0257

Gnomad ASJ exome

AF:

0.0644

Gnomad EAS exome

AF:

0.000544

Gnomad FIN exome

AF:

0.0240

Gnomad NFE exome

AF:

0.0610

Gnomad OTH exome

AF:

0.0489

GnomAD4 exome

AF:

0.0599

AC:

87530

AN:

1461844

Hom.:

2934

Cov.:

AF XY:

0.0604

AC XY:

43900

AN XY:

727222

show subpopulations

African (AFR)

AF:

0.00738

AC:

247

AN:

33480

American (AMR)

AF:

0.0276

AC:

1234

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.0637

AC:

1664

AN:

26136

East Asian (EAS)

AF:

0.000605

AC:

AN:

39698

South Asian (SAS)

AF:

0.0748

AC:

6452

AN:

86254

European-Finnish (FIN)

AF:

0.0267

AC:

1425

AN:

53386

Middle Eastern (MID)

AF:

0.0553

AC:

319

AN:

5768

European-Non Finnish (NFE)

AF:

0.0656

AC:

72910

AN:

1112002

Other (OTH)

AF:

0.0539

AC:

3255

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.477

Heterozygous variant carriers

5045

10090

15136

20181

25226

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2706

5412

8118

10824

13530

<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:

0.0415

AC:

6323

AN:

152196

Hom.:

214

Cov.:

AF XY:

0.0388

AC XY:

2887

AN XY:

74420

show subpopulations

African (AFR)

AF:

0.0111

AC:

463

AN:

41536

American (AMR)

AF:

0.0308

AC:

470

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.0631

AC:

219

AN:

3472

East Asian (EAS)

AF:

0.00135

AC:

AN:

5188

South Asian (SAS)

AF:

0.0605

AC:

291

AN:

4812

European-Finnish (FIN)

AF:

0.0231

AC:

245

AN:

10598

Middle Eastern (MID)

AF:

0.0510

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0644

AC:

4378

AN:

68002

Other (OTH)

AF:

0.0464

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

291

582

874

1165

1456

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

156

234

312

390

<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:

0.0487

Hom.:

232

Bravo

AF:

0.0398

TwinsUK

AF:

0.0639

AC:

237

ALSPAC

AF:

0.0636

AC:

245

ESP6500AA

AF:

0.0118

AC:

ESP6500EA

AF:

0.0626

AC:

538

ExAC

AF:

0.0475

AC:

5768

Asia WGS

AF:

0.0240

AC:

AN:

3478

EpiCase

AF:

0.0594

EpiControl

AF:

0.0625

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.078

BayesDel_addAF

Benign

-0.66

BayesDel_noAF

Benign

-0.66

CADD

Benign

0.030

(source)

DANN

Benign

0.31

DEOGEN2

Benign

0.029

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.029

LIST_S2

Benign

0.040

MetaRNN

Benign

0.0032

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.0

PhyloP100

-0.85

PrimateAI

Benign

0.28

PROVEAN

Benign

-0.30

REVEL

Benign

0.097

Sift

Benign

1.0

Sift4G

Benign

1.0

Polyphen

0.84

Vest4

0.023

MPC

0.074

ClinPred

0.0095

GERP RS

-0.66

Varity_R

0.029

gMVP

0.092

Mutation Taster

=100/0

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over