rs1204402

chrX-100638897-G-A

Variant summary

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

The ENST00000494424.1(TSPAN6):n.47+1048C>T variant causes a intron, non coding transcript change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0741 in 110,728 control chromosomes in the GnomAD database, including 625 homozygotes. There are 2,200 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 0.074 (625 hom., 2200 hem., cov: 22)
• Consequence: TSPAN6 ENST00000494424.1 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.150

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=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.229 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TSPAN6	ENST00000494424.1	n.47+1048C>T		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.0739 AC: 8183 AN: 110677 Hom.: 626 Cov.: 22 AF XY: 0.0662 AC XY: 2181 AN XY: 32937

Gnomad AFR AF: 0.234

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0309

Gnomad ASJ AF: 0.00530

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00154

Gnomad FIN AF: 0.0142

Gnomad MID AF: 0.00422

Gnomad NFE AF: 0.0116

Gnomad OTH AF: 0.0589

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

GnomAD4 genome AF: 0.0741 AC: 8205 AN: 110728 Hom.: 625 Cov.: 22 AF XY: 0.0667 AC XY: 2200 AN XY: 32998

Gnomad4 AFR AF: 0.234

Gnomad4 AMR AF: 0.0309

Gnomad4 ASJ AF: 0.00530

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00154

Gnomad4 FIN AF: 0.0142

Gnomad4 NFE AF: 0.0116

Gnomad4 OTH AF: 0.0582

Alfa AF: 0.0428 Hom.: 488

Bravo AF: 0.0831

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
Cadd	Benign	0.36
Dann	Benign	0.57

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs1204402; hg19: chrX-99893894;