12-3178113-G-T

Variant names:

• chr12-3178113-G-T
• rs878962
• NM_006675.5:c.-17-23064G>T

Variant summary

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

The NM_006675.5(TSPAN9):​c.-17-23064G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.487 in 151,972 control chromosomes in the GnomAD database, including 18,510 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 0.49 (18510 hom., cov: 31)
• Consequence: TSPAN9 NM_006675.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.96
• Publications: 5 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=-0.89).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.566 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TSPAN9	NM_006675.5	c.-17-23064G>T		intron_variant	Intron 2 of 8	ENST00000011898.10	NP_006666.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TSPAN9	ENST00000011898.10	c.-17-23064G>T		intron_variant	Intron 2 of 8	1	NM_006675.5	ENSP00000011898.5
TSPAN9	ENST00000537971.5	c.-17-23064G>T		intron_variant	Intron 1 of 7	3		ENSP00000444799.1
TSPAN9	ENST00000649909.1	c.-130+94394G>T		intron_variant	Intron 2 of 6			ENSP00000497370.1
TSPAN9	ENST00000444315.6	n.-17-23064G>T		intron_variant	Intron 2 of 5	4		ENSP00000412908.2

Frequencies

GnomAD3 genomes AF: 0.487 AC: 73951 AN: 151854 Hom.: 18490 Cov.: 31

Gnomad AFR AF: 0.385

Gnomad AMI AF: 0.388

Gnomad AMR AF: 0.575

Gnomad ASJ AF: 0.555

Gnomad EAS AF: 0.522

Gnomad SAS AF: 0.550

Gnomad FIN AF: 0.516

Gnomad MID AF: 0.415

Gnomad NFE AF: 0.516

Gnomad OTH AF: 0.498

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

GnomAD4 genome AF: 0.487 AC: 74003 AN: 151972 Hom.: 18510 Cov.: 31 AF XY: 0.489 AC XY: 36361 AN XY: 74296

African (AFR) AF: 0.384 AC: 15922 AN: 41424

American (AMR) AF: 0.576 AC: 8810 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.555 AC: 1923 AN: 3466

East Asian (EAS) AF: 0.522 AC: 2690 AN: 5158

South Asian (SAS) AF: 0.550 AC: 2640 AN: 4804

European-Finnish (FIN) AF: 0.516 AC: 5452 AN: 10568

Middle Eastern (MID) AF: 0.418 AC: 123 AN: 294

European-Non Finnish (NFE) AF: 0.516 AC: 35037 AN: 67952

Other (OTH) AF: 0.499 AC: 1052 AN: 2110

Alfa AF: 0.490 Hom.: 23798

Bravo AF: 0.490

Asia WGS AF: 0.524 AC: 1823 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.087
DANN	Benign	0.54
PhyloP100		-2.0
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: rs878962; hg19: chr12-3287279;