NM_003270.4:c.669+652A>G

Variant names:

• chrX-100631833-T-C
• rs1204399
• NM_003270.4:c.669+652A>G

Variant summary

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

The NM_003270.4(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 NM_003270.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00400
• Publications: 6 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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.73 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003270.4. 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
	TSPAN6	NM_003270.4	MANE Select	c.669+652A>G		intron	N/A	NP_003261.1
	TSPAN6	NM_001278740.2		c.405+652A>G		intron	N/A	NP_001265669.1
	TSPAN6	NM_001278741.1		c.405+652A>G		intron	N/A	NP_001265670.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TSPAN6	ENST00000373020.9	TSL:1 MANE Select	c.669+652A>G		intron	N/A	ENSP00000362111.4
	TSPAN6	ENST00000867886.1		c.669+652A>G		intron	N/A	ENSP00000537945.1
	TSPAN6	ENST00000867889.1		c.669+652A>G		intron	N/A	ENSP00000537948.1

Frequencies

GnomAD3 genomes AF: 0.462 AC: 50953 AN: 110190 Hom.: 9125 Cov.: 22

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

African (AFR) AF: 0.624 AC: 18878 AN: 30276

American (AMR) AF: 0.482 AC: 4959 AN: 10298

Ashkenazi Jewish (ASJ) AF: 0.439 AC: 1148 AN: 2615

East Asian (EAS) AF: 0.754 AC: 2629 AN: 3485

South Asian (SAS) AF: 0.411 AC: 1056 AN: 2567

European-Finnish (FIN) AF: 0.320 AC: 1859 AN: 5818

Middle Eastern (MID) AF: 0.449 AC: 96 AN: 214

European-Non Finnish (NFE) AF: 0.366 AC: 19305 AN: 52797

Other (OTH) AF: 0.492 AC: 742 AN: 1508

Alfa AF: 0.411 Hom.: 36631

Bravo AF: 0.492

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.61
DANN	Benign	0.74
PhyloP100		-0.0040
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: rs1204399; hg19: chrX-99886830;