chr12-3260008-T-C

Position:

• chr12-3260008-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.64-18413T>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

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]

TSPAN9 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TSPAN9	NM_006675.5	c.64-18413T>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.64-18413T>C		intron_variant		1	NM_006675.5	ENSP00000011898.5

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

Gnomad4 AFR AF: 0.111

Gnomad4 AMR AF: 0.456

Gnomad4 ASJ AF: 0.315

Gnomad4 EAS AF: 0.415

Gnomad4 SAS AF: 0.495

Gnomad4 FIN AF: 0.433

Gnomad4 NFE AF: 0.501

Gnomad4 OTH AF: 0.378

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	4.2
DANN	Benign	0.76

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: rs1860436; hg19: chr12-3369174;