10-69483850-C-A

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong

The NM_012339.5(TSPAN15):​c.256C>A​(p.Arg86Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Consequence

TSPAN15
NM_012339.5 missense

Scores

10
7
2

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.19
Variant links:
Genes affected
TSPAN15 (HGNC:23298): (tetraspanin 15) 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. The use of alternate polyadenylation sites has been found for this gene. [provided by RefSeq, Jul 2008]

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ACMG classification

Classification made for transcript

Verdict is Likely_pathogenic. Variant got 6 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.969

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
TSPAN15NM_012339.5 linkc.256C>A p.Arg86Ser missense_variant Exon 2 of 8 ENST00000373290.7 NP_036471.1 O95858

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
TSPAN15ENST00000373290.7 linkc.256C>A p.Arg86Ser missense_variant Exon 2 of 8 1 NM_012339.5 ENSP00000362387.2 O95858
TSPAN15ENST00000475069.5 linkn.26C>A non_coding_transcript_exon_variant Exon 1 of 6 3
TSPAN15ENST00000478112.1 linkn.374C>A non_coding_transcript_exon_variant Exon 2 of 2 2
TSPAN15ENST00000452130.1 linkc.-18C>A upstream_gene_variant 5 ENSP00000404528.1 H7C285

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
31
GnomAD4 genome
Cov.:
32

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Feb 15, 2025
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.256C>A (p.R86S) alteration is located in exon 2 (coding exon 2) of the TSPAN15 gene. This alteration results from a C to A substitution at nucleotide position 256, causing the arginine (R) at amino acid position 86 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
Pathogenic
0.98
BayesDel_addAF
Pathogenic
0.35
D
BayesDel_noAF
Pathogenic
0.26
CADD
Pathogenic
29
DANN
Uncertain
1.0
DEOGEN2
Uncertain
0.48
T
Eigen
Pathogenic
0.73
Eigen_PC
Uncertain
0.64
FATHMM_MKL
Benign
0.70
D
LIST_S2
Uncertain
0.92
D
M_CAP
Uncertain
0.17
D
MetaRNN
Pathogenic
0.97
D
MetaSVM
Uncertain
0.53
D
MutationAssessor
Pathogenic
3.1
M
PrimateAI
Uncertain
0.65
T
PROVEAN
Pathogenic
-5.5
D
REVEL
Pathogenic
0.76
Sift
Pathogenic
0.0
D
Sift4G
Pathogenic
0.0
D
Polyphen
1.0
D
Vest4
0.94
MutPred
0.85
Loss of stability (P = 0.1394);
MVP
0.78
MPC
1.2
ClinPred
1.0
D
GERP RS
3.7
Varity_R
0.96
gMVP
0.88

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.

Other links and lift over

hg19: chr10-71243606; API