chrX-100630848-C-T

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The NM_003270.4(TSPAN6):​c.688G>A​(p.Ala230Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000108 in 1,205,126 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 3 hemizygotes in GnomAD. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000027 (0 hom., 1 hem., cov: 23)
  • Exomes 𝑓: 0.0000091 (0 hom. 2 hem.)
• Consequence: TSPAN6 NM_003270.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• 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: Likely_benign. The variant received -4 ACMG points.

• BS2: High Hemizygotes in GnomAdExome4 at 2 gene

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TSPAN6	NM_003270.4	MANE Select	c.688G>A	p.Ala230Thr	missense	Exon 7 of 8	NP_003261.1	O43657
	TSPAN6	NM_001278740.2		c.424G>A	p.Ala142Thr	missense	Exon 7 of 8	NP_001265669.1
	TSPAN6	NM_001278741.1		c.424G>A	p.Ala142Thr	missense	Exon 7 of 8	NP_001265670.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TSPAN6	ENST00000373020.9	TSL:1 MANE Select	c.688G>A	p.Ala230Thr	missense	Exon 7 of 8	ENSP00000362111.4	O43657
	TSPAN6	ENST00000867886.1		c.688G>A	p.Ala230Thr	missense	Exon 7 of 7	ENSP00000537945.1
	TSPAN6	ENST00000867889.1		c.688G>A	p.Ala230Thr	missense	Exon 7 of 8	ENSP00000537948.1

Frequencies

GnomAD3 genomes AF: 0.0000268 AC: 3 AN: 111786 Hom.: 0 Cov.: 23

Gnomad AFR AF: 0.0000325

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000376

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000110 AC: 2 AN: 181760 AF XY: 0.00

Gnomad AFR exome AF: 0.0000764

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000124

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000915 AC: 10 AN: 1093340 Hom.: 0 Cov.: 28 AF XY: 0.00000557 AC XY: 2 AN XY: 358858

African (AFR) AF: 0.0000380 AC: 1 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: 0.00000955 AC: 8 AN: 837925

Other (OTH) AF: 0.0000218 AC: 1 AN: 45925

GnomAD4 genome AF: 0.0000268 AC: 3 AN: 111786 Hom.: 0 Cov.: 23 AF XY: 0.0000294 AC XY: 1 AN XY: 34008

African (AFR) AF: 0.0000325 AC: 1 AN: 30779

American (AMR) AF: 0.00 AC: 0 AN: 10493

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2639

East Asian (EAS) AF: 0.00 AC: 0 AN: 3581

South Asian (SAS) AF: 0.00 AC: 0 AN: 2685

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6037

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 239

European-Non Finnish (NFE) AF: 0.0000376 AC: 2 AN: 53158

Other (OTH) AF: 0.00 AC: 0 AN: 1494

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000264

ExAC AF: 0.00000824 AC: 1

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.56
BayesDel_addAF	Benign	-0.079	T
BayesDel_noAF	Benign	-0.16
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.15	T
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Benign	0.85	D
M_CAP	Uncertain	0.18	D
MetaRNN	Uncertain	0.59	D
MetaSVM	Uncertain	0.27	D
MutationAssessor	Uncertain	2.0	M
PhyloP100		2.6
PrimateAI	Uncertain	0.58	T
PROVEAN	Uncertain	-2.6	D
REVEL	Uncertain	0.63
Sift	Uncertain	0.0030	D
Sift4G	Uncertain	0.0050	D
Polyphen		1.0	D
Vest4		0.46
MutPred		0.79		Loss of stability (P = 0.0979)
MVP		0.59
MPC		0.32
ClinPred		0.50	D
GERP RS		5.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.43
gMVP		0.93
Mutation Taster		=97/3	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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;