rs1860436

Variant names:

• chr12-3260008-T-C
• rs1860436
• NM_006675.5:c.64-18413T>C

Variant summary

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

The NM_006675.5(TSPAN9):​c.64-18413T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.375 in 152,144 control chromosomes in the GnomAD database, including 12,907 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 0.38 (12907 hom., cov: 33)
• Consequence: TSPAN9 NM_006675.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.88
• Publications: 2 publications found

Genes affected

TSPAN9 (HGNC:21640): (tetraspanin 9) 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. Alternatively spliced transcripts encoding the same protein have been identified. [provided by RefSeq, Nov 2009]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.497 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006675.5. 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
	TSPAN9	NM_006675.5	MANE Select	c.64-18413T>C		intron	N/A	NP_006666.1
	TSPAN9	NM_001168320.2		c.64-18413T>C		intron	N/A	NP_001161792.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TSPAN9	ENST00000011898.10	TSL:1 MANE Select	c.64-18413T>C		intron	N/A	ENSP00000011898.5
	TSPAN9	ENST00000407263.2	TSL:5	c.64-18413T>C		intron	N/A	ENSP00000384488.1
	TSPAN9	ENST00000537971.5	TSL:3	c.64-18413T>C		intron	N/A	ENSP00000444799.1

Frequencies

GnomAD3 genomes AF: 0.376 AC: 57116 AN: 152026 Hom.: 12899 Cov.: 33

Gnomad AFR AF: 0.112

Gnomad AMI AF: 0.410

Gnomad AMR AF: 0.455

Gnomad ASJ AF: 0.315

Gnomad EAS AF: 0.414

Gnomad SAS AF: 0.495

Gnomad FIN AF: 0.433

Gnomad MID AF: 0.348

Gnomad NFE AF: 0.501

Gnomad OTH AF: 0.378

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

GnomAD4 genome AF: 0.376 AC: 57130 AN: 152144 Hom.: 12907 Cov.: 33 AF XY: 0.373 AC XY: 27730 AN XY: 74358

African (AFR) AF: 0.111 AC: 4622 AN: 41534

American (AMR) AF: 0.456 AC: 6982 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.315 AC: 1094 AN: 3472

East Asian (EAS) AF: 0.415 AC: 2135 AN: 5148

South Asian (SAS) AF: 0.495 AC: 2384 AN: 4816

European-Finnish (FIN) AF: 0.433 AC: 4578 AN: 10578

Middle Eastern (MID) AF: 0.350 AC: 103 AN: 294

European-Non Finnish (NFE) AF: 0.501 AC: 34060 AN: 67978

Other (OTH) AF: 0.378 AC: 799 AN: 2112

Alfa AF: 0.417 Hom.: 2873

Bravo AF: 0.365

Asia WGS AF: 0.473 AC: 1646 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	4.2
DANN	Benign	0.76
PhyloP100		-2.9
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: rs1860436; hg19: chr12-3369174;