Variant rs28381981 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.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. 15/20 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 0.042 ( 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

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:

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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=0.0032238066).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0628 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.1255C>T	p.His419Tyr	missense_variant	8/8	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.1255C>T	p.His419Tyr	missense_variant	8/8	2	NM_033034.3	ENSP00000369373.3		Q9C035-1
ENSG00000239920	ENST00000380259.7 linkuse as main transcript	n.231+13168C>T		intron_variant		5		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

GnomAD3 exomes

AF:

0.0465

AC:

11679

AN:

251370

Hom.:

368

AF XY:

0.0494

AC XY:

6713

AN XY:

135858

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 SAS exome

AF:

0.0730

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

Gnomad4 AFR exome

AF:

0.00738

Gnomad4 AMR exome

AF:

0.0276

Gnomad4 ASJ exome

AF:

0.0637

Gnomad4 EAS exome

AF:

0.000605

Gnomad4 SAS exome

AF:

0.0748

Gnomad4 FIN exome

AF:

0.0267

Gnomad4 NFE exome

AF:

0.0656

Gnomad4 OTH exome

AF:

0.0539

GnomAD4 genome

AF:

0.0415

AC:

6323

AN:

152196

Hom.:

214

Cov.:

AF XY:

0.0388

AC XY:

2887

AN XY:

74420

show subpopulations

Gnomad4 AFR

AF:

0.0111

Gnomad4 AMR

AF:

0.0308

Gnomad4 ASJ

AF:

0.0631

Gnomad4 EAS

AF:

0.00135

Gnomad4 SAS

AF:

0.0605

Gnomad4 FIN

AF:

0.0231

Gnomad4 NFE

AF:

0.0644

Gnomad4 OTH

AF:

0.0464

Alfa

AF:

0.0546

Hom.:

151

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 v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.078

BayesDel_addAF

Benign

-0.66

BayesDel_noAF

Benign

-0.66

CADD

Benign

0.030

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

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

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

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