Variant chr6-30164010-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_033229.3(TRIM15):c.326C>T(p.Pro109Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000484 in 1,613,038 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00032 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00050 ( 7 hom. )

Consequence

TRIM15
NM_033229.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.784

Variant links:

Genes affected

TRIM15 (HGNC:16284): (tripartite motif containing 15) 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 localizes to the cytoplasm. Alternatively spliced transcript variants have been described, but their biological validity has not been determined. [provided by RefSeq, Jul 2008]

TRIM15 links:

TRIM10 (HGNC:):

TRIM10 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.018742085).

BS2

High Homozygotes in GnomAdExome4 at 7 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TRIM15	NM_033229.3 linkuse as main transcript	c.326C>T	p.Pro109Leu	missense_variant	1/7	ENST00000376694.9	NP_150232.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TRIM15	ENST00000376694.9 linkuse as main transcript	c.326C>T	p.Pro109Leu	missense_variant	1/7	1	NM_033229.3	ENSP00000365884	P1	Q9C019-1
TRIM15	ENST00000619857.4 linkuse as main transcript	c.119C>T	p.Pro40Leu	missense_variant	1/8	5		ENSP00000484001

Frequencies

GnomAD3 genomes

AF:

0.000322

AC:

AN:

152156

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000145

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000720

Gnomad ASJ

AF:

0.00144

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000208

Gnomad FIN

AF:

0.000188

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.000309

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000516

AC:

126

AN:

244358

Hom.:

AF XY:

0.000532

AC XY:

AN XY:

133390

show subpopulations

Gnomad AFR exome

AF:

0.000132

Gnomad AMR exome

AF:

0.000493

Gnomad ASJ exome

AF:

0.00151

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000296

Gnomad FIN exome

AF:

0.000231

Gnomad NFE exome

AF:

0.000636

Gnomad OTH exome

AF:

0.00148

GnomAD4 exome

AF:

0.000500

AC:

731

AN:

1460764

Hom.:

Cov.:

AF XY:

0.000524

AC XY:

381

AN XY:

726696

show subpopulations

Gnomad4 AFR exome

AF:

0.000956

Gnomad4 AMR exome

AF:

0.000671

Gnomad4 ASJ exome

AF:

0.00111

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000290

Gnomad4 FIN exome

AF:

0.000229

Gnomad4 NFE exome

AF:

0.000435

Gnomad4 OTH exome

AF:

0.000927

GnomAD4 genome

AF:

0.000322

AC:

AN:

152274

Hom.:

Cov.:

AF XY:

0.000363

AC XY:

AN XY:

74460

show subpopulations

Gnomad4 AFR

AF:

0.000144

Gnomad4 AMR

AF:

0.000719

Gnomad4 ASJ

AF:

0.00144

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000208

Gnomad4 FIN

AF:

0.000188

Gnomad4 NFE

AF:

0.000309

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.000624

Hom.:

Bravo

AF:

0.000325

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000554

AC:

ExAC

AF:

0.000525

AC:

Asia WGS

AF:

0.00231

AC:

AN:

3478

EpiCase

AF:

0.000763

EpiControl

AF:

0.000889

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 01, 2021

The c.326C>T (p.P109L) alteration is located in exon 1 (coding exon 1) of the TRIM15 gene. This alteration results from a C to T substitution at nucleotide position 326, causing the proline (P) at amino acid position 109 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.16

BayesDel_addAF

Benign

-0.53

BayesDel_noAF

Benign

-0.63

CADD

Benign

DANN

Benign

0.70

DEOGEN2

Benign

0.029

T;T

Eigen

Benign

-0.60

Eigen_PC

Benign

-0.59

FATHMM_MKL

Benign

0.13

M_CAP

Benign

0.064

MetaRNN

Benign

0.019

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.2

.;L

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.41

PROVEAN

Benign

-1.9

.;N

REVEL

Benign

0.15

Sift

Benign

0.59

.;T

Sift4G

Benign

0.66

T;T

Polyphen

0.14

.;B

Vest4

0.096

MVP

0.60

MPC

1.2

ClinPred

0.034

GERP RS

4.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.098

gMVP

0.28

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over