NM_012339.5:c.649C>T

Variant names:

• chr10-69506154-C-T
• rs200107830
• NM_012339.5:c.649C>T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 1P and 0B. PP3

The NM_012339.5(TSPAN15):​c.649C>T​(p.Arg217Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000186 in 1,614,010 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00013 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00019 (0 hom.)
• Consequence: TSPAN15 NM_012339.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.06
• Publications: 0 publications found

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]

ACMG classification

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

• PP3: MetaRNN computational evidence supports a deleterious effect, 0.825

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_012339.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TSPAN15	NM_012339.5	MANE Select	c.649C>T	p.Arg217Trp	missense	Exon 7 of 8	NP_036471.1	O95858
	TSPAN15	NM_001351263.2		c.388C>T	p.Arg130Trp	missense	Exon 5 of 6	NP_001338192.1
	TSPAN15	NR_147091.2		n.850C>T		non_coding_transcript_exon	Exon 7 of 8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TSPAN15	ENST00000373290.7	TSL:1 MANE Select	c.649C>T	p.Arg217Trp	missense	Exon 7 of 8	ENSP00000362387.2	O95858
	TSPAN15	ENST00000858304.1		c.715C>T	p.Arg239Trp	missense	Exon 7 of 8	ENSP00000528363.1
	TSPAN15	ENST00000954128.1		c.664C>T	p.Arg222Trp	missense	Exon 7 of 8	ENSP00000624187.1

Frequencies

GnomAD3 genomes AF: 0.000131 AC: 20 AN: 152172 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000483

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: 0.000265

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000115 AC: 29 AN: 251444 AF XY: 0.000103

Gnomad AFR exome AF: 0.0000615

Gnomad AMR exome AF: 0.0000289

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000544

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000229

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000192 AC: 281 AN: 1461838 Hom.: 0 Cov.: 31 AF XY: 0.000193 AC XY: 140 AN XY: 727222

African (AFR) AF: 0.000119 AC: 4 AN: 33480

American (AMR) AF: 0.0000224 AC: 1 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.0000756 AC: 3 AN: 39698

South Asian (SAS) AF: 0.00 AC: 0 AN: 86248

European-Finnish (FIN) AF: 0.0000187 AC: 1 AN: 53414

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.000239 AC: 266 AN: 1111978

Other (OTH) AF: 0.0000994 AC: 6 AN: 60392

GnomAD4 genome AF: 0.000131 AC: 20 AN: 152172 Hom.: 0 Cov.: 33 AF XY: 0.0000942 AC XY: 7 AN XY: 74346

African (AFR) AF: 0.0000483 AC: 2 AN: 41434

American (AMR) AF: 0.00 AC: 0 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5196

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10610

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.000265 AC: 18 AN: 68030

Other (OTH) AF: 0.00 AC: 0 AN: 2090

Alfa AF: 0.000267 Hom.: 0

Bravo AF: 0.000166

TwinsUK AF: 0.00 AC: 0

ALSPAC AF: 0.000259 AC: 1

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000349 AC: 3

ExAC AF: 0.0000576 AC: 7

EpiCase AF: 0.000164

EpiControl AF: 0.000296

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.59
BayesDel_addAF	Pathogenic	0.16	D
BayesDel_noAF	Pathogenic	0.30
CADD	Pathogenic	29
DANN	Pathogenic	1.0
DEOGEN2	Uncertain	0.61	D
Eigen	Uncertain	0.61
Eigen_PC	Uncertain	0.55
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Pathogenic	0.97	D
M_CAP	Uncertain	0.16	D
MetaRNN	Pathogenic	0.82	D
MetaSVM	Uncertain	0.45	D
MutationAssessor	Uncertain	2.5	M
PhyloP100		2.1
PrimateAI	Uncertain	0.67	T
PROVEAN	Pathogenic	-5.6	D
REVEL	Pathogenic	0.77
Sift	Uncertain	0.0030	D
Sift4G	Uncertain	0.0030	D
Polyphen		1.0	D
Vest4		0.86
MVP		0.71
MPC		1.2
ClinPred		0.83	D
GERP RS		4.6
Varity_R		0.55
gMVP		0.88
Mutation Taster		=86/14	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs200107830; hg19: chr10-71265910; COSMIC: COSV64783393;