chr10-69483874-G-C

Position:

• chr10-69483874-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_012339.5(TSPAN15):​c.280G>C​(p.Ala94Pro) variant causes a missense, splice region 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. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: TSPAN15 NM_012339.5 missense, splice_region
• Scores: Splicing: ADA: 0.000007838
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.56

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]

TSPAN15 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.924

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TSPAN15	NM_012339.5	c.280G>C	p.Ala94Pro	missense_variant, splice_region_variant	2/8	ENST00000373290.7	NP_036471.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TSPAN15	ENST00000373290.7	c.280G>C	p.Ala94Pro	missense_variant, splice_region_variant	2/8	1	NM_012339.5	ENSP00000362387.2
TSPAN15	ENST00000452130.1	c.7G>C	p.Ala3Pro	missense_variant, splice_region_variant	1/7	5		ENSP00000404528.1
TSPAN15	ENST00000475069.5	n.50G>C		splice_region_variant, non_coding_transcript_exon_variant	1/6	3
TSPAN15	ENST00000478112.1	n.398G>C		non_coding_transcript_exon_variant	2/2	2

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

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 06, 2024

The c.280G>C (p.A94P) alteration is located in exon 2 (coding exon 2) of the TSPAN15 gene. This alteration results from a G to C substitution at nucleotide position 280, causing the alanine (A) at amino acid position 94 to be replaced by a proline (P). 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	0.81
BayesDel_addAF	Uncertain	0.14	D
BayesDel_noAF	Uncertain	-0.040
CADD	Benign	17
DANN	Uncertain	0.99
DEOGEN2	Benign	0.15	T;.
Eigen	Benign	-0.39
Eigen_PC	Benign	-0.45
FATHMM_MKL	Uncertain	0.86	D
LIST_S2	Benign	0.82	T;T
M_CAP	Benign	0.072	D
MetaRNN	Pathogenic	0.92	D;D
MetaSVM	Benign	-0.38	T
MutationAssessor	Uncertain	2.2	M;.
PrimateAI	Benign	0.39	T
PROVEAN	Benign	-2.1	N;N
REVEL	Pathogenic	0.66
Sift	Benign	0.048	D;T
Sift4G	Benign	0.29	T;T
Polyphen		0.68	P;.
Vest4		0.79
MutPred		0.79		Loss of stability (P = 0.1247);.;
MVP		0.48
MPC		0.79
ClinPred		0.43	T
GERP RS		-2.0
Varity_R		0.36
gMVP		0.93

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.0000078
dbscSNV1_RF	Benign	0.048
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: chr10-71243630;