dbSNP rs774511407: TSPAN8:p.Glu140Asp (chr12-71137977-T-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_004616.3(TSPAN8):c.420A>T(p.Glu140Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000821 in 1,461,408 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 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: not found (cov: 33)

Exomes 𝑓: 0.0000082 ( 0 hom. )

Consequence

TSPAN8
NM_004616.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.371

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 made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.110372245).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TSPAN8	NM_004616.3 link	c.420A>T	p.Glu140Asp	missense_variant	Exon 6 of 9	ENST00000247829.8	NP_004607.1	P19075
TSPAN8	NM_001369760.1 link	c.420A>T	p.Glu140Asp	missense_variant	Exon 5 of 8		NP_001356689.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
TSPAN8	ENST00000247829.8 link	c.420A>T	p.Glu140Asp	missense_variant	Exon 6 of 9	1	NM_004616.3	ENSP00000247829.3	P19075
TSPAN8	ENST00000393330.6 link	c.420A>T	p.Glu140Asp	missense_variant	Exon 9 of 12	1		ENSP00000377003.2	P19075
TSPAN8	ENST00000546561.2 link	c.420A>T	p.Glu140Asp	missense_variant	Exon 5 of 8	1		ENSP00000447160.1	P19075
TSPAN8	ENST00000552128.2 link	n.284A>T		non_coding_transcript_exon_variant	Exon 3 of 6	3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000821

AC:

AN:

1461408

Hom.:

Cov.:

AF XY:

0.00000688

AC XY:

AN XY:

726986

show subpopulations

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:

0.0000108

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.18

BayesDel_noAF

Benign

-0.50

CADD

Benign

2.0

DANN

Benign

0.94

DEOGEN2

Benign

0.024

T;T;T

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.047

LIST_S2

Benign

0.30

.;.;T

M_CAP

Benign

0.017

MetaRNN

Benign

0.11

T;T;T

MetaSVM

Benign

-0.99

MutationAssessor

Benign

1.7

L;L;L

PrimateAI

Benign

0.29

PROVEAN

Benign

-0.53

N;N;N

REVEL

Benign

0.10

Sift

Benign

0.44

T;T;T

Sift4G

Benign

0.44

T;T;T

Polyphen

0.0040

B;B;B

Vest4

0.13

MutPred

0.47

Gain of ubiquitination at K136 (P = 0.0913);Gain of ubiquitination at K136 (P = 0.0913);Gain of ubiquitination at K136 (P = 0.0913);

MVP

0.70

MPC

0.080

ClinPred

0.046

GERP RS

-2.6

Varity_R

0.052

gMVP

0.41

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

Computational scores

Splicing

Publications

Other links and lift over