rs767197012

Variant names:

• chrX-100630848-C-A
• rs767197012
• NM_003270.4:c.688G>T

Your query was ambiguous. Multiple possible variants found:

• chrX-100630848-C-A
• chrX-100630848-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_003270.4(TSPAN6):​c.688G>T​(p.Ala230Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000915 in 1,093,340 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A230T) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 23)
  • Exomes 𝑓: 9.1e-7 (0 hom. 0 hem.)
• Consequence: TSPAN6 NM_003270.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.62
• 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: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3225941).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TSPAN6	NM_003270.4	c.688G>T	p.Ala230Ser	missense_variant	Exon 7 of 8	ENST00000373020.9	NP_003261.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TSPAN6	ENST00000373020.9	c.688G>T	p.Ala230Ser	missense_variant	Exon 7 of 8	1	NM_003270.4	ENSP00000362111.4
TSPAN6	ENST00000612152.4	c.340G>T	p.Ala114Ser	missense_variant	Exon 6 of 7	5		ENSP00000482130.1

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome AF: 9.15e-7 AC: 1 AN: 1093340 Hom.: 0 Cov.: 28 AF XY: 0.00 AC XY: 0 AN XY: 358858

African (AFR) AF: 0.00 AC: 0 AN: 26308

American (AMR) AF: 0.00 AC: 0 AN: 35179

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19345

East Asian (EAS) AF: 0.00 AC: 0 AN: 30164

South Asian (SAS) AF: 0.00 AC: 0 AN: 53867

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40499

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4128

European-Non Finnish (NFE) AF: 0.00000119 AC: 1 AN: 837925

Other (OTH) AF: 0.00 AC: 0 AN: 45925

GnomAD4 genome Cov.: 23

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.41
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.10	.;T
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Benign	0.75	T;D
M_CAP	Uncertain	0.091	D
MetaRNN	Benign	0.32	T;T
MetaSVM	Uncertain	-0.11	T
MutationAssessor	Benign	1.3	.;L
PhyloP100		2.6
PrimateAI	Uncertain	0.55	T
PROVEAN	Benign	-1.2	.;N
REVEL	Uncertain	0.43
Sift	Benign	0.37	.;T
Sift4G	Benign	0.11	T;T
Polyphen		0.87	.;P
Vest4		0.20
MutPred		0.76		.;Loss of stability (P = 0.1564);
MVP		0.45
MPC		0.27
ClinPred		0.92	D
GERP RS		5.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.17
gMVP		0.84
Mutation Taster		=87/13	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs767197012; hg19: chrX-99885845;