Genetic Variant TSPAN15:p.Gly110Ser (chr10-69485186-G-A) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_012339.5(TSPAN15):c.328G>A(p.Gly110Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000882 in 1,614,148 control chromosomes in the GnomAD database, including 2 homozygotes. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00027 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00095 ( 2 hom. )

Consequence

TSPAN15
NM_012339.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 9.28

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BS2

High Homozygotes in GnomAdExome4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TSPAN15	NM_012339.5 link	c.328G>A	p.Gly110Ser	missense_variant	Exon 3 of 8	ENST00000373290.7	NP_036471.1	O95858

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
TSPAN15	ENST00000373290.7 link	c.328G>A	p.Gly110Ser	missense_variant	Exon 3 of 8	1	NM_012339.5	ENSP00000362387.2	O95858
TSPAN15	ENST00000452130.1 link	c.55G>A	p.Gly19Ser	missense_variant	Exon 2 of 7	5		ENSP00000404528.1	H7C285
TSPAN15	ENST00000475069.5 link	n.98G>A		non_coding_transcript_exon_variant	Exon 2 of 6	3

Frequencies

GnomAD3 genomes

AF:

0.000269

AC:

AN:

152148

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000145

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.000514

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000398

AC:

100

AN:

251492

Hom.:

AF XY:

0.000397

AC XY:

AN XY:

135920

show subpopulations

Gnomad AFR exome

AF:

0.0000615

Gnomad AMR exome

AF:

0.0000578

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:

0.000844

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.000945

AC:

1382

AN:

1461882

Hom.:

Cov.:

AF XY:

0.000883

AC XY:

642

AN XY:

727244

show subpopulations

Gnomad4 AFR exome

AF:

0.0000597

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.0000383

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000187

Gnomad4 NFE exome

AF:

0.00120

Gnomad4 OTH exome

AF:

0.000662

GnomAD4 genome

AF:

0.000269

AC:

AN:

152266

Hom.:

Cov.:

AF XY:

0.000188

AC XY:

AN XY:

74446

show subpopulations

Gnomad4 AFR

AF:

0.000144

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000515

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000603

Hom.:

Bravo

AF:

0.000302

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00156

AC:

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.000581

AC:

ExAC

AF:

0.000362

AC:

EpiCase

AF:

0.000654

EpiControl

AF:

0.000771

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Jun 11, 2021

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.328G>A (p.G110S) 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 328, causing the glycine (G) at amino acid position 110 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

Benign

0.29

BayesDel_addAF

Uncertain

0.069

BayesDel_noAF

Pathogenic

0.30

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.37

T;.

Eigen

Pathogenic

0.80

Eigen_PC

Pathogenic

0.78

FATHMM_MKL

Pathogenic

1.0

LIST_S2

Uncertain

0.91

D;D

M_CAP

Benign

0.072

MetaRNN

Uncertain

0.70

D;D

MetaSVM

Uncertain

0.32

MutationAssessor

Pathogenic

3.0

M;.

PrimateAI

Uncertain

0.60

PROVEAN

Uncertain

-3.8

D;D

REVEL

Pathogenic

0.84

Sift

Benign

0.091

T;D

Sift4G

Benign

0.097

T;T

Polyphen

0.99

D;.

Vest4

0.68

MVP

0.77

MPC

1.0

ClinPred

0.49

GERP RS

5.3

Varity_R

0.51

gMVP

0.93

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

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