chr6-30168441-A-T

Position:

chr6-30168441-A-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_033229.3(TRIM15):c.619A>T(p.Thr207Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000239 in 1,612,548 control chromosomes in the GnomAD database, including 28 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 Likely benign (★).

Frequency

Genomes: 𝑓 0.00030 ( 5 hom., cov: 32)

Exomes 𝑓: 0.00023 ( 23 hom. )

Consequence

TRIM15
NM_033229.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.14

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0048574805).

BP6

Variant 6-30168441-A-T is Benign according to our data. Variant chr6-30168441-A-T is described in ClinVar as [Likely_benign]. Clinvar id is 2360671.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 5 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
TRIM15	NM_033229.3 linkuse as main transcript	c.619A>T	p.Thr207Ser	missense_variant	3/7	ENST00000376694.9	NP_150232.2
TRIM15	XM_011514987.2 linkuse as main transcript	c.304A>T	p.Thr102Ser	missense_variant	4/8		XP_011513289.1
TRIM15	XM_047419503.1 linkuse as main transcript	c.619A>T	p.Thr207Ser	missense_variant	3/5		XP_047275459.1
TRIM15	XM_011514988.3 linkuse as main transcript	c.12A>T	p.Ser4=	synonymous_variant	1/5		XP_011513290.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TRIM15	ENST00000376694.9 linkuse as main transcript	c.619A>T	p.Thr207Ser	missense_variant	3/7	1	NM_033229.3	ENSP00000365884	P1	Q9C019-1
TRIM15	ENST00000619857.4 linkuse as main transcript	c.412A>T	p.Thr138Ser	missense_variant	3/8	5		ENSP00000484001
TRIM15	ENST00000433744.1 linkuse as main transcript	c.130A>T	p.Thr44Ser	missense_variant	1/5	3		ENSP00000398285

Frequencies

GnomAD3 genomes

AF:

0.000204

AC:

AN:

152208

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000850

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00250

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00191

GnomAD3 exomes

AF:

0.000216

AC:

AN:

245332

Hom.:

AF XY:

0.000172

AC XY:

AN XY:

133810

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000291

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00175

Gnomad SAS exome

AF:

0.0000662

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000908

Gnomad OTH exome

AF:

0.00132

GnomAD4 exome

AF:

0.000234

AC:

341

AN:

1460222

Hom.:

Cov.:

AF XY:

0.000208

AC XY:

151

AN XY:

726406

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000269

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00149

Gnomad4 SAS exome

AF:

0.0000348

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000108

Gnomad4 OTH exome

AF:

0.00422

GnomAD4 genome

AF:

0.000295

AC:

AN:

152326

Hom.:

Cov.:

AF XY:

0.000107

AC XY:

AN XY:

74492

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000849

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00251

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00851

Alfa

AF:

0.0000869

Hom.:

Bravo

AF:

0.000317

ExAC

AF:

0.000170

AC:

Asia WGS

AF:

0.0260

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 29, 2021

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.56

BayesDel_noAF

Benign

-0.59

CADD

Benign

0.19

DANN

Benign

0.82

DEOGEN2

Benign

0.0070

T;T

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.019

M_CAP

Benign

0.016

MetaRNN

Benign

0.0049

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.53

.;N

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.30

PROVEAN

Benign

-0.54

.;N

REVEL

Benign

0.089

Sift

Benign

0.50

.;T

Sift4G

Benign

0.44

T;T

Polyphen

0.0

.;B

Vest4

0.035

MutPred

0.30

.;Loss of phosphorylation at T207 (P = 0.0738);

MVP

0.42

MPC

0.36

ClinPred

0.032

GERP RS

-2.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.027

gMVP

0.037

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