Variant 12-57746249-G-C details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_005981.5(TSPAN31):c.305G>C(p.Ser102Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000155 in 1,613,706 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. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000015 ( 0 hom. )

Consequence

TSPAN31
NM_005981.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.539

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 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=0.11853996).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
TSPAN31	NM_005981.5 linkuse as main transcript	c.305G>C	p.Ser102Thr	missense_variant	3/6	ENST00000257910.8	NP_005972.1
TSPAN31	NM_001330169.2 linkuse as main transcript	c.71G>C	p.Ser24Thr	missense_variant	3/6		NP_001317098.1
TSPAN31	XM_024449123.2 linkuse as main transcript	c.71G>C	p.Ser24Thr	missense_variant	3/6		XP_024304891.1
TSPAN31	NM_001330168.2 linkuse as main transcript	c.64-340G>C		intron_variant			NP_001317097.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TSPAN31	ENST00000257910.8 linkuse as main transcript	c.305G>C	p.Ser102Thr	missense_variant	3/6	1	NM_005981.5	ENSP00000257910	P1

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

152160

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

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:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000239

AC:

AN:

251468

Hom.:

AF XY:

0.00000736

AC XY:

AN XY:

135914

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000116

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000879

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.0000151

AC:

AN:

1461546

Hom.:

Cov.:

AF XY:

0.00000963

AC XY:

AN XY:

727100

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000201

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:

0.00000720

Gnomad4 OTH exome

AF:

0.0000828

GnomAD4 genome

AF:

0.0000197

AC:

AN:

152160

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74340

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000567

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

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 20, 2021

The c.305G>C (p.S102T) alteration is located in exon 3 (coding exon 3) of the TSPAN31 gene. This alteration results from a G to C substitution at nucleotide position 305, causing the serine (S) at amino acid position 102 to be replaced by a threonine (T). 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

0.088

BayesDel_addAF

Benign

-0.25

BayesDel_noAF

Benign

-0.38

CADD

Benign

DANN

Benign

0.82

DEOGEN2

Benign

0.11

T;.;T

Eigen

Benign

-0.47

Eigen_PC

Benign

-0.34

FATHMM_MKL

Uncertain

0.78

LIST_S2

Benign

0.35

T;T;T

M_CAP

Benign

0.020

MetaRNN

Benign

0.12

T;T;T

MetaSVM

Benign

-0.94

MutationAssessor

Benign

0.66

N;.;.

MutationTaster

Benign

1.0

D;D;N

PrimateAI

Benign

0.42

PROVEAN

Benign

-0.80

N;N;N

REVEL

Benign

0.083

Sift

Benign

0.35

T;T;T

Sift4G

Benign

0.26

T;T;T

Polyphen

0.071

B;.;.

Vest4

0.32

MutPred

0.34

Loss of glycosylation at S102 (P = 0.0703);.;.;

MVP

0.69

MPC

0.32

ClinPred

0.039

GERP RS

0.95

Varity_R

0.059

gMVP

0.52

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.060

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over