Variant 12-71129383-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -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. 16/21 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

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 Likely_benign. Variant got -4 ACMG points.

BP4

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TSPAN8	NM_004616.3 link	c.608C>A	p.Ala203Glu	missense_variant	Exon 8 of 9	ENST00000247829.8	NP_004607.1	P19075
TSPAN8	NM_001369760.1 link	c.608C>A	p.Ala203Glu	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.608C>A	p.Ala203Glu	missense_variant	Exon 8 of 9	1	NM_004616.3	ENSP00000247829.3	P19075
TSPAN8	ENST00000393330.6 link	c.608C>A	p.Ala203Glu	missense_variant	Exon 11 of 12	1		ENSP00000377003.2	P19075
TSPAN8	ENST00000546561.2 link	c.608C>A	p.Ala203Glu	missense_variant	Exon 7 of 8	1		ENSP00000447160.1	P19075
TSPAN8	ENST00000552128.2 link	n.472C>A		non_coding_transcript_exon_variant	Exon 5 of 6	3

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

150154

Hom.:

Cov.:

FAILED QC

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

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

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

Gnomad4 AFR

AF:

0.00

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:

0.00

Gnomad4 OTH

AF:

0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Jun 29, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.608C>A (p.A203E) alteration is located in exon 8 (coding exon 7) of the TSPAN8 gene. This alteration results from a C to A substitution at nucleotide position 608, causing the alanine (A) at amino acid position 203 to be replaced by a glutamic acid (E). 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

0.10

BayesDel_addAF

Benign

-0.22

BayesDel_noAF

Benign

-0.55

CADD

Benign

0.061

DANN

Benign

0.22

DEOGEN2

Benign

0.017

T;T;T

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.6

FATHMM_MKL

Benign

0.0077

LIST_S2

Benign

0.25

.;.;T

M_CAP

Benign

0.020

MetaRNN

Benign

0.048

T;T;T

MetaSVM

Benign

-0.76

MutationAssessor

Benign

-0.42

N;N;N

PrimateAI

Benign

0.30

PROVEAN

Benign

1.7

N;N;N

REVEL

Benign

0.27

Sift

Benign

1.0

T;T;T

Sift4G

Benign

0.78

T;T;T

Polyphen

0.0

B;B;B

Vest4

0.055

MutPred

0.49

Loss of ubiquitination at K204 (P = 0.0736);Loss of ubiquitination at K204 (P = 0.0736);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

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over