dbSNP rs753456818: TSPAN31:p.Ala15Thr (chr12-57745197-G-A) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_005981.5(TSPAN31):c.43G>A(p.Ala15Thr) variant causes a missense change. The variant allele was found at a frequency of 0.00000657 in 152,180 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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. A15S) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Consequence

TSPAN31
NM_005981.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.71

Publications

1 publications found

Variant links:

Genes affected

TSPAN31 (HGNC:10539): (tetraspanin 31) 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 thought to be involved in growth-related cellular processes. This gene is associated with tumorigenesis and osteosarcoma. [provided by RefSeq, Jul 2008]

TSPAN31 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.3858596).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TSPAN31	NM_005981.5 link	c.43G>A	p.Ala15Thr	missense_variant	Exon 1 of 6	ENST00000257910.8	NP_005972.1	Q12999
TSPAN31	NM_001330168.2 link	c.43G>A	p.Ala15Thr	missense_variant	Exon 1 of 4		NP_001317097.1	Q12999F8VWE0
TSPAN31	NM_001330169.2 link	c.-206G>A		5_prime_UTR_variant	Exon 1 of 6		NP_001317098.1	Q12999B4DFJ7
TSPAN31	XM_024449123.2 link	c.-414G>A		upstream_gene_variant			XP_024304891.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TSPAN31	ENST00000257910.8 link	c.43G>A	p.Ala15Thr	missense_variant	Exon 1 of 6	1	NM_005981.5	ENSP00000257910.3		Q12999

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152180

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

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

Cov.:

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152180

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74336

show subpopulations

African (AFR)

AF:

0.0000241

AC:

AN:

41446

American (AMR)

AF:

0.00

AC:

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5182

South Asian (SAS)

AF:

0.00

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10620

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68034

Other (OTH)

AF:

0.00

AC:

AN:

2086

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.25

BayesDel_addAF

Uncertain

0.078

BayesDel_noAF

Benign

-0.13

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.24

T;T;T

Eigen

Uncertain

0.34

Eigen_PC

Uncertain

0.41

FATHMM_MKL

Uncertain

0.86

LIST_S2

Uncertain

0.96

D;D;D

M_CAP

Uncertain

0.11

MetaRNN

Benign

0.39

T;T;T

MetaSVM

Benign

-0.34

MutationAssessor

Uncertain

2.2

M;.;.

PhyloP100

3.7

PrimateAI

Uncertain

0.72

PROVEAN

Uncertain

-2.7

D;D;D

REVEL

Uncertain

0.43

Sift

Benign

0.11

T;D;D

Sift4G

Benign

0.13

T;T;D

Polyphen

0.94

P;P;.

Vest4

0.44

MutPred

0.54

Loss of ubiquitination at K10 (P = 0.1037);Loss of ubiquitination at K10 (P = 0.1037);Loss of ubiquitination at K10 (P = 0.1037);

MVP

0.82

MPC

0.91

ClinPred

0.99

GERP RS

5.0

PromoterAI

-0.11

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.6

Varity_R

0.53

gMVP

0.40

Mutation Taster

=55/45

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

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over