X-100638897-G-A

Variant names:

• chrX-100638897-G-A
• rs1204402
• ENST00000494424.1:n.47+1048C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000494424.1(TSPAN6):​n.47+1048C>T variant causes a intron 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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.150
• Publications: 0 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000494424.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TSPAN6	ENST00000494424.1	TSL:2	n.47+1048C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0739 AC: 8183 AN: 110677 Hom.: 626 Cov.: 22

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

African (AFR) AF: 0.234 AC: 7082 AN: 30268

American (AMR) AF: 0.0309 AC: 319 AN: 10337

Ashkenazi Jewish (ASJ) AF: 0.00530 AC: 14 AN: 2641

East Asian (EAS) AF: 0.00 AC: 0 AN: 3559

South Asian (SAS) AF: 0.00154 AC: 4 AN: 2592

European-Finnish (FIN) AF: 0.0142 AC: 84 AN: 5913

Middle Eastern (MID) AF: 0.00463 AC: 1 AN: 216

European-Non Finnish (NFE) AF: 0.0116 AC: 613 AN: 53006

Other (OTH) AF: 0.0582 AC: 88 AN: 1513

Alfa AF: 0.0455 Hom.: 606

Bravo AF: 0.0831

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.36
DANN	Benign	0.57
PhyloP100		0.15

Splicing

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

Other links and lift over

dbSNP: rs1204402; hg19: chrX-99893894;