Genetic Variant TSPAN8:p.Val229Ile (chr12-71125363-C-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_004616.3(TSPAN8):c.685G>A(p.Val229Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 17/22 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 variant affecting the same amino acid position, but resulting in a different missense (i.e. V229F) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Consequence

TSPAN8
NM_004616.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.484

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:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.16162378).

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.685G>A	p.Val229Ile	missense	Exon 9 of 9	NP_004607.1	P19075
	TSPAN8	NM_001369760.1		c.685G>A	p.Val229Ile	missense	Exon 8 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.685G>A	p.Val229Ile	missense	Exon 9 of 9	ENSP00000247829.3	P19075
TSPAN8	ENST00000393330.6	TSL:1	c.685G>A	p.Val229Ile	missense	Exon 12 of 12	ENSP00000377003.2	P19075
TSPAN8	ENST00000546561.2	TSL:1	c.685G>A	p.Val229Ile	missense	Exon 8 of 8	ENSP00000447160.1	P19075

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000400

AC:

AN:

250100

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000546

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000824

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.22

BayesDel_noAF

Benign

-0.38

CADD

Benign

(source)

DANN

Benign

0.94

DEOGEN2

Benign

0.026

Eigen

Benign

-0.33

Eigen_PC

Benign

-0.19

FATHMM_MKL

Benign

0.53

LIST_S2

Benign

0.72

M_CAP

Benign

0.025

MetaRNN

Benign

0.16

MetaSVM

Benign

-0.89

MutationAssessor

Benign

1.2

PhyloP100

0.48

PrimateAI

Benign

0.37

PROVEAN

Benign

-0.35

REVEL

Benign

0.14

Sift

Benign

0.40

Sift4G

Benign

0.14

Polyphen

0.076

Vest4

0.025

MutPred

0.55

Loss of catalytic residue at V229 (P = 0.0439)

MVP

0.62

MPC

0.078

ClinPred

0.14

GERP RS

2.0

Varity_R

0.064

gMVP

0.13

Mutation Taster

=89/11

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

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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