Genetic Variant TSPAN8:p.Ser213Ala (chr12-71129354-A-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_004616.3(TSPAN8):c.637T>G(p.Ser213Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.375 in 1,572,296 control chromosomes in the GnomAD database, including 115,695 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.32 ( 8469 hom., cov: 31)

Exomes 𝑓: 0.38 ( 107226 hom. )

Consequence

TSPAN8
NM_004616.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.60

Publications

47 publications found

Variant links:

Genes affected

TSPAN8 (HGNC:11855): (tetraspanin 8) 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. This encoded protein is a cell surface glycoprotein that is known to complex with integrins. This gene is expressed in different carcinomas. The use of alternate polyadenylation sites has been found for this gene. [provided by RefSeq, Jul 2008]

TSPAN8 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0029125214).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.405 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TSPAN8	NM_004616.3 link	c.637T>G	p.Ser213Ala	missense_variant	Exon 8 of 9	ENST00000247829.8	NP_004607.1	P19075
TSPAN8	NM_001369760.1 link	c.637T>G	p.Ser213Ala	missense_variant	Exon 7 of 8		NP_001356689.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
TSPAN8	ENST00000247829.8 link	c.637T>G	p.Ser213Ala	missense_variant	Exon 8 of 9	1	NM_004616.3	ENSP00000247829.3	P19075
TSPAN8	ENST00000393330.6 link	c.637T>G	p.Ser213Ala	missense_variant	Exon 11 of 12	1		ENSP00000377003.2	P19075
TSPAN8	ENST00000546561.2 link	c.637T>G	p.Ser213Ala	missense_variant	Exon 7 of 8	1		ENSP00000447160.1	P19075
TSPAN8	ENST00000552128.2 link	n.501T>G		non_coding_transcript_exon_variant	Exon 5 of 6	3

Frequencies

GnomAD3 genomes

AF:

0.318

AC:

47910

AN:

150822

Hom.:

8464

Cov.:

show subpopulations

Gnomad AFR

AF:

0.174

Gnomad AMI

AF:

0.518

Gnomad AMR

AF:

0.260

Gnomad ASJ

AF:

0.447

Gnomad EAS

AF:

0.304

Gnomad SAS

AF:

0.278

Gnomad FIN

AF:

0.333

Gnomad MID

AF:

0.382

Gnomad NFE

AF:

0.409

Gnomad OTH

AF:

0.344

GnomAD2 exomes

AF:

0.336

AC:

76898

AN:

229084

AF XY:

0.347

show subpopulations

Gnomad AFR exome

AF:

0.159

Gnomad AMR exome

AF:

0.169

Gnomad ASJ exome

AF:

0.426

Gnomad EAS exome

AF:

0.295

Gnomad FIN exome

AF:

0.354

Gnomad NFE exome

AF:

0.412

Gnomad OTH exome

AF:

0.360

GnomAD4 exome

AF:

0.381

AC:

542199

AN:

1421378

Hom.:

107226

Cov.:

AF XY:

0.381

AC XY:

269447

AN XY:

706896

show subpopulations

African (AFR)

AF:

0.162

AC:

5140

AN:

31704

American (AMR)

AF:

0.186

AC:

7528

AN:

40452

Ashkenazi Jewish (ASJ)

AF:

0.435

AC:

11037

AN:

25378

East Asian (EAS)

AF:

0.308

AC:

11882

AN:

38554

South Asian (SAS)

AF:

0.289

AC:

23282

AN:

80566

European-Finnish (FIN)

AF:

0.354

AC:

18658

AN:

52650

Middle Eastern (MID)

AF:

0.392

AC:

2208

AN:

5630

European-Non Finnish (NFE)

AF:

0.406

AC:

441107

AN:

1087640

Other (OTH)

AF:

0.363

AC:

21357

AN:

58804

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.432

Heterozygous variant carriers

15296

30592

45889

61185

76481

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

13358

26716

40074

53432

66790

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.318

AC:

47922

AN:

150918

Hom.:

8469

Cov.:

AF XY:

0.313

AC XY:

23018

AN XY:

73636

show subpopulations

African (AFR)

AF:

0.174

AC:

7173

AN:

41246

American (AMR)

AF:

0.259

AC:

3949

AN:

15218

Ashkenazi Jewish (ASJ)

AF:

0.447

AC:

1549

AN:

3468

East Asian (EAS)

AF:

0.305

AC:

1571

AN:

5154

South Asian (SAS)

AF:

0.279

AC:

1340

AN:

4798

European-Finnish (FIN)

AF:

0.333

AC:

3333

AN:

10020

Middle Eastern (MID)

AF:

0.369

AC:

107

AN:

290

European-Non Finnish (NFE)

AF:

0.409

AC:

27714

AN:

67722

Other (OTH)

AF:

0.342

AC:

715

AN:

2092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.510

Heterozygous variant carriers

1579

3159

4738

6318

7897

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

488

976

1464

1952

2440

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.387

Hom.:

41968

Bravo

AF:

0.307

TwinsUK

AF:

0.413

AC:

1531

ALSPAC

AF:

0.419

AC:

1614

ESP6500AA

AF:

0.189

AC:

832

ESP6500EA

AF:

0.410

AC:

3526

ExAC

AF:

0.341

AC:

41401

Asia WGS

AF:

0.260

AC:

900

AN:

3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.070

BayesDel_addAF

Benign

-0.63

BayesDel_noAF

Benign

-0.54

CADD

Benign

(source)

DANN

Benign

0.36

DEOGEN2

Benign

0.018

T;T;T

Eigen

Benign

-0.98

Eigen_PC

Benign

-0.61

FATHMM_MKL

Benign

0.016

LIST_S2

Benign

0.17

.;.;T

MetaRNN

Benign

0.0029

T;T;T

MetaSVM

Benign

-0.96

MutationAssessor

Benign

-2.8

N;N;N

PhyloP100

1.6

PrimateAI

Uncertain

0.49

PROVEAN

Benign

1.7

N;N;N

REVEL

Benign

0.25

Sift

Benign

1.0

T;T;T

Sift4G

Benign

1.0

T;T;T

Polyphen

0.0

B;B;B

Vest4

0.027

MPC

0.072

ClinPred

0.0023

GERP RS

4.9

Varity_R

0.11

gMVP

0.72

Mutation Taster

=99/1

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over