Genetic Variant TSPAN8:p.Ala203Glu (chr12-71129383-G-T) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_004616.3(TSPAN8):c.608C>A(p.Ala203Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

TSPAN8
NM_004616.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.440

Publications

0 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: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.048283428).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004616.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TSPAN8	NM_004616.3	MANE Select	c.608C>A	p.Ala203Glu	missense	Exon 8 of 9	NP_004607.1	P19075
	TSPAN8	NM_001369760.1		c.608C>A	p.Ala203Glu	missense	Exon 7 of 8	NP_001356689.1	P19075

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TSPAN8	ENST00000247829.8	TSL:1 MANE Select	c.608C>A	p.Ala203Glu	missense	Exon 8 of 9	ENSP00000247829.3	P19075
TSPAN8	ENST00000393330.6	TSL:1	c.608C>A	p.Ala203Glu	missense	Exon 11 of 12	ENSP00000377003.2	P19075
TSPAN8	ENST00000546561.2	TSL:1	c.608C>A	p.Ala203Glu	missense	Exon 7 of 8	ENSP00000447160.1	P19075

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

150154

Hom.:

Cov.:

Gnomad AFR

AF:

0.00

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AC0;AS_VQSR

AF:

0.00

AC:

AN:

1431872

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

711674

African (AFR)

AF:

0.00

AC:

AN:

31492

American (AMR)

AF:

0.00

AC:

AN:

39444

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25430

East Asian (EAS)

AF:

0.00

AC:

AN:

38760

South Asian (SAS)

AF:

0.00

AC:

AN:

80234

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52862

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5642

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1098884

Other (OTH)

AF:

0.00

AC:

AN:

59124

GnomAD4 genome

Data not reliable, filtered out with message: AC0;AS_VQSR

AF:

0.00

AC:

AN:

150154

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

73158

African (AFR)

AF:

0.00

AC:

AN:

40846

American (AMR)

AF:

0.00

AC:

AN:

15096

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3462

East Asian (EAS)

AF:

0.00

AC:

AN:

5146

South Asian (SAS)

AF:

0.00

AC:

AN:

4776

European-Finnish (FIN)

AF:

0.00

AC:

AN:

9852

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67688

Other (OTH)

AF:

0.00

AC:

AN:

2062

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.22

BayesDel_noAF

Benign

-0.55

CADD

Benign

0.061

(source)

DANN

Benign

0.22

DEOGEN2

Benign

0.017

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.6

FATHMM_MKL

Benign

0.0077

LIST_S2

Benign

0.25

M_CAP

Benign

0.020

MetaRNN

Benign

0.048

MetaSVM

Benign

-0.76

MutationAssessor

Benign

-0.42

PhyloP100

-0.44

PrimateAI

Benign

0.30

PROVEAN

Benign

1.7

REVEL

Benign

0.27

Sift

Benign

1.0

Sift4G

Benign

0.78

Polyphen

0.0

Vest4

0.055

MutPred

0.49

Loss of ubiquitination at K204 (P = 0.0736)

MVP

0.34

MPC

0.10

ClinPred

0.039

GERP RS

-8.0

Varity_R

0.060

gMVP

0.48

Mutation Taster

=93/7

polymorphism

(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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over