Variant rs1051334 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -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. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

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

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 made for transcript

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
TSPAN8	NM_004616.3 linkuse as main transcript	c.637T>G	p.Ser213Ala	missense_variant	8/9	ENST00000247829.8	NP_004607.1
TSPAN8	NM_001369760.1 linkuse as main transcript	c.637T>G	p.Ser213Ala	missense_variant	7/8		NP_001356689.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
TSPAN8	ENST00000247829.8 linkuse as main transcript	c.637T>G	p.Ser213Ala	missense_variant	8/9	1	NM_004616.3	ENSP00000247829	P1
TSPAN8	ENST00000393330.6 linkuse as main transcript	c.637T>G	p.Ser213Ala	missense_variant	11/12	1		ENSP00000377003	P1
TSPAN8	ENST00000546561.2 linkuse as main transcript	c.637T>G	p.Ser213Ala	missense_variant	7/8	1		ENSP00000447160	P1
TSPAN8	ENST00000552128.2 linkuse as main transcript	n.501T>G		non_coding_transcript_exon_variant	5/6	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

GnomAD3 exomes

AF:

0.336

AC:

76898

AN:

229084

Hom.:

14288

AF XY:

0.347

AC XY:

42987

AN XY:

124008

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 SAS exome

AF:

0.287

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

Gnomad4 AFR exome

AF:

0.162

Gnomad4 AMR exome

AF:

0.186

Gnomad4 ASJ exome

AF:

0.435

Gnomad4 EAS exome

AF:

0.308

Gnomad4 SAS exome

AF:

0.289

Gnomad4 FIN exome

AF:

0.354

Gnomad4 NFE exome

AF:

0.406

Gnomad4 OTH exome

AF:

0.363

GnomAD4 genome

AF:

0.318

AC:

47922

AN:

150918

Hom.:

8469

Cov.:

AF XY:

0.313

AC XY:

23018

AN XY:

73636

show subpopulations

Gnomad4 AFR

AF:

0.174

Gnomad4 AMR

AF:

0.259

Gnomad4 ASJ

AF:

0.447

Gnomad4 EAS

AF:

0.305

Gnomad4 SAS

AF:

0.279

Gnomad4 FIN

AF:

0.333

Gnomad4 NFE

AF:

0.409

Gnomad4 OTH

AF:

0.342

Alfa

AF:

0.396

Hom.:

30676

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

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

MutationTaster

Benign

1.0

P;P;P;P

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

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over