rs1204399

Positions:

• chrX-100631833-T-C

Variant summary

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

The ENST00000373020.9(TSPAN6):​c.669+652A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.463 in 110,242 control chromosomes in the GnomAD database, including 9,130 homozygotes. There are 14,655 hemizygotes in GnomAD. 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 0.46 (9130 hom., 14655 hem., cov: 22)
• Consequence: TSPAN6 ENST00000373020.9 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00400

Genes affected

TSPAN6 (HGNC:11858): (tetraspanin 6) 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. The protein encoded by this gene is a cell surface glycoprotein and is highly similar in sequence to the transmembrane 4 superfamily member 2 protein. It functions as a negative regulator of retinoic acid-inducible gene I-like receptor-mediated immune signaling via its interaction with the mitochondrial antiviral signaling-centered signalosome. This gene uses alternative polyadenylation sites, and multiple transcript variants result from alternative splicing. [provided by RefSeq, Jul 2013]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.73 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TSPAN6	NM_003270.4	c.669+652A>G		intron_variant		ENST00000373020.9	NP_003261.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TSPAN6	ENST00000373020.9	c.669+652A>G		intron_variant		1	NM_003270.4	ENSP00000362111	P1
TSPAN6	ENST00000612152.4	c.322-967A>G		intron_variant		5		ENSP00000482130

Frequencies

GnomAD3 genomes AF: 0.462 AC: 50953 AN: 110190 Hom.: 9125 Cov.: 22 AF XY: 0.450 AC XY: 14623 AN XY: 32470

Gnomad AFR AF: 0.623

Gnomad AMI AF: 0.486

Gnomad AMR AF: 0.482

Gnomad ASJ AF: 0.439

Gnomad EAS AF: 0.754

Gnomad SAS AF: 0.412

Gnomad FIN AF: 0.320

Gnomad MID AF: 0.453

Gnomad NFE AF: 0.366

Gnomad OTH AF: 0.489

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

GnomAD4 genome AF: 0.463 AC: 50995 AN: 110242 Hom.: 9130 Cov.: 22 AF XY: 0.450 AC XY: 14655 AN XY: 32532

Gnomad4 AFR AF: 0.624

Gnomad4 AMR AF: 0.482

Gnomad4 ASJ AF: 0.439

Gnomad4 EAS AF: 0.754

Gnomad4 SAS AF: 0.411

Gnomad4 FIN AF: 0.320

Gnomad4 NFE AF: 0.366

Gnomad4 OTH AF: 0.492

Alfa AF: 0.394 Hom.: 24397

Bravo AF: 0.492

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.61
DANN	Benign	0.74

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: rs1204399; hg19: chrX-99886830;