Variant 12-71897916-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001146213.3(TBC1D15):c.1158G>T(p.Arg386Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000347 in 1,612,528 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00028 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00035 ( 0 hom. )

Consequence

TBC1D15
NM_001146213.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.0350

Variant links:

Genes affected

TBC1D15 (HGNC:25694): (TBC1 domain family member 15) This gene encodes a member of the Ras-like proteins in brain-GTPase activating protein superfamily that share a conserved Tre-2/Bub2/Cdc16 domain. The encoded protein interacts with Ras-like protein in brain 5A and may function as a regulator of intracellular trafficking. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Apr 2009]

TBC1D15 links:

TBC1D15 (HGNC:):

TBC1D15 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.025924623).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TBC1D15	NM_001146213.3 linkuse as main transcript	c.1158G>T	p.Arg386Ser	missense_variant	10/17	ENST00000485960.7	NP_001139685.2	Q8TC07-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TBC1D15	ENST00000485960.7 linkuse as main transcript	c.1158G>T	p.Arg386Ser	missense_variant	10/17	1	NM_001146213.3	ENSP00000420678.2		Q8TC07-2

Frequencies

GnomAD3 genomes

AF:

0.000283

AC:

AN:

152034

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000965

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000327

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000501

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000255

AC:

AN:

250806

Hom.:

AF XY:

0.000236

AC XY:

AN XY:

135598

show subpopulations

Gnomad AFR exome

AF:

0.0000616

Gnomad AMR exome

AF:

0.000203

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000459

Gnomad OTH exome

AF:

0.000654

GnomAD4 exome

AF:

0.000354

AC:

517

AN:

1460376

Hom.:

Cov.:

AF XY:

0.000340

AC XY:

247

AN XY:

726556

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.000201

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000445

Gnomad4 OTH exome

AF:

0.000182

GnomAD4 genome

AF:

0.000283

AC:

AN:

152152

Hom.:

Cov.:

AF XY:

0.000255

AC XY:

AN XY:

74380

show subpopulations

Gnomad4 AFR

AF:

0.0000962

Gnomad4 AMR

AF:

0.000327

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000501

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000294

Hom.:

Bravo

AF:

0.000329

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00105

AC:

ExAC

AF:

0.000280

AC:

EpiCase

AF:

0.000709

EpiControl

AF:

0.000474

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

Aug 16, 2022

The c.1209G>T (p.R403S) alteration is located in exon 11 (coding exon 11) of the TBC1D15 gene. This alteration results from a G to T substitution at nucleotide position 1209, causing the arginine (R) at amino acid position 403 to be replaced by a serine (S). 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

Pathogenic

0.78

BayesDel_addAF

Benign

-0.41

BayesDel_noAF

Benign

-0.49

CADD

Benign

DANN

Benign

0.92

DEOGEN2

Benign

0.021

T;.;.

Eigen

Benign

-0.78

Eigen_PC

Benign

-0.66

FATHMM_MKL

Benign

0.27

LIST_S2

Uncertain

0.90

D;D;D

M_CAP

Benign

0.015

MetaRNN

Benign

0.026

T;T;T

MetaSVM

Benign

-0.92

MutationAssessor

Benign

0.11

N;.;.

PrimateAI

Pathogenic

0.79

PROVEAN

Benign

-0.48

N;N;N

REVEL

Benign

0.20

Sift

Benign

0.68

T;T;T

Sift4G

Benign

0.71

T;T;T

Polyphen

0.19

B;.;B

Vest4

0.52

MutPred

0.45

Gain of phosphorylation at R403 (P = 0.0022);.;.;

MVP

0.28

MPC

0.36

ClinPred

0.022

GERP RS

0.40

Varity_R

0.13

gMVP

0.69

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