chr12-3275588-T-C

Variant names:

• chr12-3275588-T-C
• rs527346
• NM_006675.5:c.64-2833T>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.64-2833T>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
• Publications: 1 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=-1.06).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.451 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TSPAN9	NM_006675.5	MANE Select	c.64-2833T>C		intron	N/A	NP_006666.1	O75954
	TSPAN9	NM_001168320.2		c.64-2833T>C		intron	N/A	NP_001161792.1	O75954

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TSPAN9	ENST00000011898.10	TSL:1 MANE Select	c.64-2833T>C		intron	N/A	ENSP00000011898.5	O75954
	TSPAN9	ENST00000407263.2	TSL:5	c.64-2833T>C		intron	N/A	ENSP00000384488.1	B5MD23
	TSPAN9	ENST00000865934.1		c.64-2833T>C		intron	N/A	ENSP00000535993.1

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

African (AFR) AF: 0.400 AC: 16614 AN: 41546

American (AMR) AF: 0.419 AC: 6409 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.611 AC: 2118 AN: 3468

East Asian (EAS) AF: 0.227 AC: 1175 AN: 5184

South Asian (SAS) AF: 0.348 AC: 1682 AN: 4830

European-Finnish (FIN) AF: 0.539 AC: 5723 AN: 10614

Middle Eastern (MID) AF: 0.531 AC: 156 AN: 294

European-Non Finnish (NFE) AF: 0.455 AC: 30964 AN: 68004

Other (OTH) AF: 0.461 AC: 974 AN: 2114

Alfa AF: 0.426 Hom.: 7192

Bravo AF: 0.426

Asia WGS AF: 0.300 AC: 1042 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.1
CADD	Benign	0.055
DANN	Benign	0.38
PhyloP100		-2.5
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: rs527346; hg19: chr12-3384754;