dbSNP rs205498: TRIM25:p.Pro358Leu (chr17-56901433-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_005082.5(TRIM25):c.1073C>T(p.Pro358Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.742 in 1,613,540 control chromosomes in the GnomAD database, including 445,607 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 the same amino acid substitution has been previously reported as Likely benign in UniProt.

Frequency

Genomes: 𝑓 0.77 ( 44882 hom., cov: 30)

Exomes 𝑓: 0.74 ( 400725 hom. )

Consequence

TRIM25
NM_005082.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0170

Variant links:

Genes affected

TRIM25 (HGNC:12932): (tripartite motif containing 25) 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 is an RNA binding protein, functions as a ubiquitin E3 ligase and is involved in multiple cellular processes, including regulation of antiviral innate immunity. [provided by RefSeq, Sep 2021]

TRIM25 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=8.9472604E-7).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.812 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRIM25	NM_005082.5 link	c.1073C>T	p.Pro358Leu	missense_variant	Exon 4 of 9	ENST00000316881.9	NP_005073.2	Q14258

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TRIM25	ENST00000316881.9 link	c.1073C>T	p.Pro358Leu	missense_variant	Exon 4 of 9	1	NM_005082.5	ENSP00000323889.4		Q14258

Frequencies

GnomAD3 genomes

AF:

0.767

AC:

116423

AN:

151884

Hom.:

44868

Cov.:

show subpopulations

Gnomad AFR

AF:

0.820

Gnomad AMI

AF:

0.669

Gnomad AMR

AF:

0.752

Gnomad ASJ

AF:

0.863

Gnomad EAS

AF:

0.833

Gnomad SAS

AF:

0.721

Gnomad FIN

AF:

0.738

Gnomad MID

AF:

0.820

Gnomad NFE

AF:

0.736

Gnomad OTH

AF:

0.766

GnomAD3 exomes

AF:

0.750

AC:

188477

AN:

251142

Hom.:

70930

AF XY:

0.749

AC XY:

101677

AN XY:

135714

show subpopulations

Gnomad AFR exome

AF:

0.821

Gnomad AMR exome

AF:

0.731

Gnomad ASJ exome

AF:

0.854

Gnomad EAS exome

AF:

0.830

Gnomad SAS exome

AF:

0.726

Gnomad FIN exome

AF:

0.744

Gnomad NFE exome

AF:

0.732

Gnomad OTH exome

AF:

0.760

GnomAD4 exome

AF:

0.740

AC:

1081518

AN:

1461538

Hom.:

400725

Cov.:

AF XY:

0.740

AC XY:

537932

AN XY:

727078

show subpopulations

Gnomad4 AFR exome

AF:

0.820

Gnomad4 AMR exome

AF:

0.728

Gnomad4 ASJ exome

AF:

0.849

Gnomad4 EAS exome

AF:

0.816

Gnomad4 SAS exome

AF:

0.726

Gnomad4 FIN exome

AF:

0.736

Gnomad4 NFE exome

AF:

0.733

Gnomad4 OTH exome

AF:

0.749

GnomAD4 genome

AF:

0.766

AC:

116478

AN:

152002

Hom.:

44882

Cov.:

AF XY:

0.767

AC XY:

56957

AN XY:

74288

show subpopulations

Gnomad4 AFR

AF:

0.820

Gnomad4 AMR

AF:

0.752

Gnomad4 ASJ

AF:

0.863

Gnomad4 EAS

AF:

0.832

Gnomad4 SAS

AF:

0.720

Gnomad4 FIN

AF:

0.738

Gnomad4 NFE

AF:

0.736

Gnomad4 OTH

AF:

0.765

Alfa

AF:

0.749

Hom.:

70217

Bravo

AF:

0.772

TwinsUK

AF:

0.737

AC:

2734

ALSPAC

AF:

0.738

AC:

2845

ESP6500AA

AF:

0.809

AC:

3565

ESP6500EA

AF:

0.739

AC:

6352

ExAC

AF:

0.748

AC:

90863

Asia WGS

AF:

0.766

AC:

2664

AN:

3478

EpiCase

AF:

0.749

EpiControl

AF:

0.750

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.083

BayesDel_addAF

Benign

-0.66

BayesDel_noAF

Benign

-0.57

CADD

Benign

DANN

Benign

0.71

DEOGEN2

Benign

0.059

T;T

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.28

LIST_S2

Benign

0.33

.;T

MetaRNN

Benign

8.9e-7

T;T

MetaSVM

Benign

-0.96

MutationAssessor

Benign

1.1

L;L

PrimateAI

Benign

0.28

PROVEAN

Benign

-1.0

N;N

REVEL

Benign

0.047

Sift

Benign

0.13

T;T

Sift4G

Benign

0.092

T;T

Polyphen

0.050

B;B

Vest4

0.022

MPC

0.24

ClinPred

0.0050

GERP RS

0.60

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.6

Varity_R

0.094

gMVP

0.17

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