Variant chr10-69485189-G-A details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_012339.5(TSPAN15):c.331G>A(p.Val111Met) variant causes a missense change. The variant allele was found at a frequency of 0.00214 in 1,614,142 control chromosomes in the GnomAD database, including 8 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0012 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0022 ( 8 hom. )

Consequence

TSPAN15
NM_012339.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.67

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 Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.055907726).

BS2

High Homozygotes in GnomAdExome4 at 8 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TSPAN15	NM_012339.5 linkuse as main transcript	c.331G>A	p.Val111Met	missense_variant	3/8	ENST00000373290.7	NP_036471.1	O95858

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
TSPAN15	ENST00000373290.7 linkuse as main transcript	c.331G>A	p.Val111Met	missense_variant	3/8	1	NM_012339.5	ENSP00000362387.2	O95858
TSPAN15	ENST00000452130.1 linkuse as main transcript	c.58G>A	p.Val20Met	missense_variant	2/7	5		ENSP00000404528.1	H7C285
TSPAN15	ENST00000475069.5 linkuse as main transcript	n.101G>A		non_coding_transcript_exon_variant	2/6	3

Frequencies

GnomAD3 genomes

AF:

0.00116

AC:

176

AN:

152152

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000314

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00137

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000577

Gnomad SAS

AF:

0.000828

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00194

Gnomad OTH

AF:

0.000958

GnomAD3 exomes

AF:

0.00121

AC:

304

AN:

251490

Hom.:

AF XY:

0.00124

AC XY:

169

AN XY:

135918

show subpopulations

Gnomad AFR exome

AF:

0.000123

Gnomad AMR exome

AF:

0.000983

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00163

Gnomad FIN exome

AF:

0.000185

Gnomad NFE exome

AF:

0.00185

Gnomad OTH exome

AF:

0.000489

GnomAD4 exome

AF:

0.00224

AC:

3281

AN:

1461872

Hom.:

Cov.:

AF XY:

0.00221

AC XY:

1610

AN XY:

727234

show subpopulations

Gnomad4 AFR exome

AF:

0.000358

Gnomad4 AMR exome

AF:

0.000805

Gnomad4 ASJ exome

AF:

0.0000383

Gnomad4 EAS exome

AF:

0.000277

Gnomad4 SAS exome

AF:

0.00173

Gnomad4 FIN exome

AF:

0.000225

Gnomad4 NFE exome

AF:

0.00267

Gnomad4 OTH exome

AF:

0.00149

GnomAD4 genome

AF:

0.00116

AC:

176

AN:

152270

Hom.:

Cov.:

AF XY:

0.000927

AC XY:

AN XY:

74454

show subpopulations

Gnomad4 AFR

AF:

0.000313

Gnomad4 AMR

AF:

0.00137

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000578

Gnomad4 SAS

AF:

0.000829

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00194

Gnomad4 OTH

AF:

0.000948

Alfa

AF:

0.00150

Hom.:

Bravo

AF:

0.00122

TwinsUK

AF:

0.00324

AC:

ALSPAC

AF:

0.00311

AC:

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00221

AC:

ExAC

AF:

0.00122

AC:

148

Asia WGS

AF:

0.00173

AC:

AN:

3478

EpiCase

AF:

0.00218

EpiControl

AF:

0.00237

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.331G>A (p.V111M) alteration is located in exon 3 (coding exon 3) of the TSPAN15 gene. This alteration results from a G to A substitution at nucleotide position 331, causing the valine (V) at amino acid position 111 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

0.15

BayesDel_addAF

Benign

-0.18

BayesDel_noAF

Uncertain

-0.030

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.36

T;.

Eigen

Uncertain

0.49

Eigen_PC

Uncertain

0.46

FATHMM_MKL

Uncertain

0.79

LIST_S2

Uncertain

0.92

D;D

M_CAP

Uncertain

0.11

MetaRNN

Benign

0.056

T;T

MetaSVM

Uncertain

0.024

MutationAssessor

Uncertain

2.7

M;.

PrimateAI

Benign

0.40

PROVEAN

Benign

-1.9

N;N

REVEL

Pathogenic

0.65

Sift

Uncertain

0.0050

D;D

Sift4G

Uncertain

0.014

D;D

Polyphen

0.96

D;.

Vest4

0.68

MVP

0.63

MPC

0.85

ClinPred

0.087

GERP RS

4.4

Varity_R

0.089

gMVP

0.79

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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