chr12-3275588-T-C

Position:

• chr12-3275588-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006675.5(TSPAN9):​c.64-2833T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.436 in 152,260 control chromosomes in the GnomAD database, including 14,734 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 0.44 (14734 hom., cov: 35)
• Consequence: TSPAN9 NM_006675.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.45

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=-1.06).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.451 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TSPAN9	NM_006675.5	c.64-2833T>C		intron_variant		ENST00000011898.10	NP_006666.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TSPAN9	ENST00000011898.10	c.64-2833T>C		intron_variant		1	NM_006675.5	ENSP00000011898	P1

Frequencies

GnomAD3 genomes AF: 0.436 AC: 66262 AN: 152142 Hom.: 14727 Cov.: 35

Gnomad AFR AF: 0.400

Gnomad AMI AF: 0.548

Gnomad AMR AF: 0.419

Gnomad ASJ AF: 0.611

Gnomad EAS AF: 0.226

Gnomad SAS AF: 0.349

Gnomad FIN AF: 0.539

Gnomad MID AF: 0.532

Gnomad NFE AF: 0.455

Gnomad OTH AF: 0.459

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

GnomAD4 genome AF: 0.436 AC: 66315 AN: 152260 Hom.: 14734 Cov.: 35 AF XY: 0.439 AC XY: 32701 AN XY: 74450

Gnomad4 AFR AF: 0.400

Gnomad4 AMR AF: 0.419

Gnomad4 ASJ AF: 0.611

Gnomad4 EAS AF: 0.227

Gnomad4 SAS AF: 0.348

Gnomad4 FIN AF: 0.539

Gnomad4 NFE AF: 0.455

Gnomad4 OTH AF: 0.461

Alfa AF: 0.421 Hom.: 6330

Bravo AF: 0.426

Asia WGS AF: 0.300 AC: 1042 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.1
CADD	Benign	0.055
DANN	Benign	0.38

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: rs527346; hg19: chr12-3384754;