12-3178113-G-T

Position:

• chr12-3178113-G-T

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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/exons	MANE	UniProt
TSPAN9	NM_006675.5	c.-17-23064G>T		intron_variant		ENST00000011898.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TSPAN9	ENST00000011898.10	c.-17-23064G>T		intron_variant		1	NM_006675.5	P1
TSPAN9	ENST00000537971.5	c.-17-23064G>T		intron_variant		3		P1
TSPAN9	ENST00000649909.1	c.-130+94394G>T		intron_variant
TSPAN9	ENST00000444315.6	c.-17-23064G>T		intron_variant, NMD_transcript_variant		4

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

Gnomad4 AFR AF: 0.384

Gnomad4 AMR AF: 0.576

Gnomad4 ASJ AF: 0.555

Gnomad4 EAS AF: 0.522

Gnomad4 SAS AF: 0.550

Gnomad4 FIN AF: 0.516

Gnomad4 NFE AF: 0.516

Gnomad4 OTH AF: 0.499

Alfa AF: 0.489 Hom.: 11200

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

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

Publications

LitVar

Other links and lift over

dbSNP: rs878962; hg19: chr12-3287279;