10-69503508-C-T

Variant names:

• chr10-69503508-C-T
• rs1227969
• NM_012339.5:c.571-930C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_012339.5(TSPAN15):​c.571-930C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.394 in 151,988 control chromosomes in the GnomAD database, including 12,259 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.39 (12259 hom., cov: 32)
• Consequence: TSPAN15 NM_012339.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0550
• Publications: 11 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.493 is higher than 0.05.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TSPAN15	NM_012339.5	MANE Select	c.571-930C>T		intron	N/A	NP_036471.1
	TSPAN15	NM_001351263.2		c.310-930C>T		intron	N/A	NP_001338192.1
	TSPAN15	NR_147091.2		n.772-930C>T		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TSPAN15	ENST00000373290.7	TSL:1 MANE Select	c.571-930C>T		intron	N/A	ENSP00000362387.2
	TSPAN15	ENST00000452130.1	TSL:5	c.298-930C>T		intron	N/A	ENSP00000404528.1
	TSPAN15	ENST00000459981.1	TSL:5	n.503-930C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.394 AC: 59831 AN: 151870 Hom.: 12242 Cov.: 32

Gnomad AFR AF: 0.498

Gnomad AMI AF: 0.467

Gnomad AMR AF: 0.355

Gnomad ASJ AF: 0.374

Gnomad EAS AF: 0.146

Gnomad SAS AF: 0.311

Gnomad FIN AF: 0.306

Gnomad MID AF: 0.433

Gnomad NFE AF: 0.378

Gnomad OTH AF: 0.386

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.394 AC: 59885 AN: 151988 Hom.: 12259 Cov.: 32 AF XY: 0.385 AC XY: 28629 AN XY: 74310

African (AFR) AF: 0.498 AC: 20648 AN: 41428

American (AMR) AF: 0.355 AC: 5418 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.374 AC: 1298 AN: 3468

East Asian (EAS) AF: 0.147 AC: 760 AN: 5176

South Asian (SAS) AF: 0.313 AC: 1504 AN: 4810

European-Finnish (FIN) AF: 0.306 AC: 3239 AN: 10576

Middle Eastern (MID) AF: 0.428 AC: 125 AN: 292

European-Non Finnish (NFE) AF: 0.378 AC: 25661 AN: 67946

Other (OTH) AF: 0.383 AC: 806 AN: 2104

Alfa AF: 0.382 Hom.: 19022

Bravo AF: 0.399

Asia WGS AF: 0.280 AC: 976 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	4.7
DANN	Benign	0.59
PhyloP100		-0.055
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1227969; hg19: chr10-71263264;