NM_005981.5:c.43G>T

Variant names:

Variant summary

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

The NM_005981.5(TSPAN31):c.43G>T(p.Ala15Ser) variant causes a missense change. The variant allele was found at a frequency of 0.0000131 in 152,180 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

TSPAN31
NM_005981.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

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:

Genome browser will be placed here

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=0.17033663).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TSPAN31	NM_005981.5 link	c.43G>T	p.Ala15Ser	missense_variant	Exon 1 of 6	ENST00000257910.8	NP_005972.1	Q12999
TSPAN31	NM_001330168.2 link	c.43G>T	p.Ala15Ser	missense_variant	Exon 1 of 4		NP_001317097.1	Q12999F8VWE0
TSPAN31	NM_001330169.2 link	c.-206G>T		5_prime_UTR_variant	Exon 1 of 6		NP_001317098.1	Q12999B4DFJ7
TSPAN31	XM_024449123.2 link	c.-414G>T		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>T	p.Ala15Ser	missense_variant	Exon 1 of 6	1	NM_005981.5	ENSP00000257910.3		Q12999

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152180

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000386

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

GnomAD2 exomes

AF:

0.00

AC:

AN:

239760

AF XY:

0.00

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1456722

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

724068

African (AFR)

AF:

0.00

AC:

AN:

33406

American (AMR)

AF:

0.00

AC:

AN:

44010

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25958

East Asian (EAS)

AF:

0.00

AC:

AN:

39596

South Asian (SAS)

AF:

0.00

AC:

AN:

85118

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53014

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5758

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1109650

Other (OTH)

AF:

0.00

AC:

AN:

60212

GnomAD4 genome

AF:

0.0000131

AC:

AN:

152180

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74336

show subpopulations

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.00

AC:

AN:

41446

American (AMR)

AF:

0.00

AC:

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.000386

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

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.275

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000756

ExAC

AF:

0.00000824

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Feb 15, 2023

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.43G>T (p.A15S) alteration is located in exon 1 (coding exon 1) of the TSPAN31 gene. This alteration results from a G to T substitution at nucleotide position 43, causing the alanine (A) at amino acid position 15 to be replaced by a serine (S). 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

0.16

BayesDel_addAF

Benign

-0.029

BayesDel_noAF

Benign

-0.28

CADD

Uncertain

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.17

T;T;T

Eigen

Benign

-0.082

Eigen_PC

Benign

0.11

FATHMM_MKL

Uncertain

0.82

LIST_S2

Uncertain

0.91

D;D;D

M_CAP

Benign

0.043

MetaRNN

Benign

0.17

T;T;T

MetaSVM

Benign

-0.63

MutationAssessor

Benign

0.69

N;.;.

PhyloP100

3.7

PrimateAI

Uncertain

0.68

PROVEAN

Benign

-1.9

N;N;N

REVEL

Uncertain

0.31

Sift

Benign

0.12

T;T;D

Sift4G

Benign

0.11

T;T;T

Polyphen

0.079

B;B;.

Vest4

0.16

MutPred

0.65

Loss of helix (P = 0.0444);Loss of helix (P = 0.0444);Loss of helix (P = 0.0444);

MVP

0.71

MPC

0.53

ClinPred

0.80

GERP RS

5.0

PromoterAI

-0.084

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.6

Varity_R

0.42

gMVP

0.37

Mutation Taster

=67/33

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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.

NM_005981.5:c.43G>T

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over