Variant 10-69506950-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong

The NM_012339.5(TSPAN15):c.857C>T(p.Thr286Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000375 in 1,609,590 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00026 ( 1 hom., cov: 33)

Exomes 𝑓: 0.00039 ( 1 hom. )

Consequence

TSPAN15
NM_012339.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.04

Variant links:

Genes affected

TSPAN15 (HGNC:23298): (tetraspanin 15) The protein encoded by this gene is a member of the transmembrane 4 superfamily, also known as the tetraspanin family. Most of these members are cell-surface proteins that are characterized by the presence of four hydrophobic domains. The proteins mediate signal transduction events that play a role in the regulation of cell development, activation, growth and motility. The use of alternate polyadenylation sites has been found for this gene. [provided by RefSeq, Jul 2008]

TSPAN15 links:

TSPAN15 (HGNC:):

TSPAN15 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.046667933).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TSPAN15	NM_012339.5 linkuse as main transcript	c.857C>T	p.Thr286Met	missense_variant	8/8	ENST00000373290.7	NP_036471.1	O95858

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TSPAN15	ENST00000373290.7 linkuse as main transcript	c.857C>T	p.Thr286Met	missense_variant	8/8	1	NM_012339.5	ENSP00000362387.2		O95858

Frequencies

GnomAD3 genomes

AF:

0.000256

AC:

AN:

152180

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000266

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000458

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000828

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000235

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000293

AC:

AN:

239160

Hom.:

AF XY:

0.000324

AC XY:

AN XY:

129668

show subpopulations

Gnomad AFR exome

AF:

0.000334

Gnomad AMR exome

AF:

0.000357

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000693

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000452

Gnomad OTH exome

AF:

0.000344

GnomAD4 exome

AF:

0.000388

AC:

565

AN:

1457292

Hom.:

Cov.:

AF XY:

0.000382

AC XY:

277

AN XY:

724414

show subpopulations

Gnomad4 AFR exome

AF:

0.000419

Gnomad4 AMR exome

AF:

0.000385

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000236

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000465

Gnomad4 OTH exome

AF:

0.000266

GnomAD4 genome

AF:

0.000256

AC:

AN:

152298

Hom.:

Cov.:

AF XY:

0.000255

AC XY:

AN XY:

74474

show subpopulations

Gnomad4 AFR

AF:

0.000265

Gnomad4 AMR

AF:

0.000457

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000829

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000235

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.000396

Hom.:

Bravo

AF:

0.000355

TwinsUK

AF:

0.000809

AC:

ALSPAC

AF:

0.000778

AC:

ESP6500AA

AF:

0.000681

AC:

ESP6500EA

AF:

0.000465

AC:

ExAC

AF:

0.000297

AC:

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

Mar 17, 2023

The c.857C>T (p.T286M) alteration is located in exon 8 (coding exon 8) of the TSPAN15 gene. This alteration results from a C to T substitution at nucleotide position 857, causing the threonine (T) at amino acid position 286 to be replaced by a methionine (M). 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

0.10

BayesDel_addAF

Benign

-0.43

BayesDel_noAF

Benign

-0.53

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.017

Eigen

Benign

-0.37

Eigen_PC

Benign

-0.40

FATHMM_MKL

Benign

0.21

LIST_S2

Uncertain

0.89

M_CAP

Benign

0.011

MetaRNN

Benign

0.047

MetaSVM

Benign

-0.95

MutationAssessor

Benign

1.4

PrimateAI

Benign

0.42

PROVEAN

Benign

-1.6

REVEL

Benign

0.080

Sift

Uncertain

0.015

Sift4G

Uncertain

0.015

Polyphen

0.80

Vest4

0.20

MVP

0.055

MPC

0.50

ClinPred

0.18

GERP RS

4.3

Varity_R

0.041

gMVP

0.55

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