X-100635575-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_003270.4(TSPAN6):c.259G>A(p.Ala87Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000511 in 1,191,957 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 205 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00056 ( 0 hom., 19 hem., cov: 23)

Exomes 𝑓: 0.00051 ( 0 hom. 186 hem. )

Consequence

TSPAN6
NM_003270.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.24

Publications

2 publications found

Variant links:

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]

TSPAN6 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.013784647).

BP6

Variant X-100635575-C-T is Benign according to our data. Variant chrX-100635575-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2661035.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Hemizygotes in GnomAd4 at 19 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TSPAN6	NM_003270.4 link	c.259G>A	p.Ala87Thr	missense_variant	Exon 2 of 8	ENST00000373020.9	NP_003261.1	O43657

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
TSPAN6	ENST00000373020.9 link	c.259G>A	p.Ala87Thr	missense_variant	Exon 2 of 8	1	NM_003270.4	ENSP00000362111.4	O43657
TSPAN6	ENST00000494424.1 link	n.531G>A		non_coding_transcript_exon_variant	Exon 3 of 6	2
TSPAN6	ENST00000496771.5 link	n.671G>A		non_coding_transcript_exon_variant	Exon 2 of 6	3
TSPAN6	ENST00000612152.4 link	c.-6G>A		5_prime_UTR_variant	Exon 2 of 7	5		ENSP00000482130.1	A0A087WYV6

Frequencies

GnomAD3 genomes

AF:

0.000562

AC:

AN:

112068

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000648

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000190

Gnomad ASJ

AF:

0.00302

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000331

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000920

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000614

AC:

103

AN:

167729

AF XY:

0.000484

show subpopulations

Gnomad AFR exome

AF:

0.0000804

Gnomad AMR exome

AF:

0.000159

Gnomad ASJ exome

AF:

0.00298

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000388

Gnomad NFE exome

AF:

0.000922

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000506

AC:

546

AN:

1079836

Hom.:

Cov.:

AF XY:

0.000534

AC XY:

186

AN XY:

348290

show subpopulations

African (AFR)

AF:

0.000116

AC:

AN:

25965

American (AMR)

AF:

0.000296

AC:

AN:

33808

Ashkenazi Jewish (ASJ)

AF:

0.00387

AC:

AN:

18856

East Asian (EAS)

AF:

0.00

AC:

AN:

29864

South Asian (SAS)

AF:

0.0000396

AC:

AN:

50527

European-Finnish (FIN)

AF:

0.000399

AC:

AN:

40148

Middle Eastern (MID)

AF:

0.000493

AC:

AN:

4055

European-Non Finnish (NFE)

AF:

0.000502

AC:

417

AN:

831274

Other (OTH)

AF:

0.000507

AC:

AN:

45339

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.480

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.000562

AC:

AN:

112121

Hom.:

Cov.:

AF XY:

0.000554

AC XY:

AN XY:

34313

show subpopulations

African (AFR)

AF:

0.0000647

AC:

AN:

30928

American (AMR)

AF:

0.000189

AC:

AN:

10561

Ashkenazi Jewish (ASJ)

AF:

0.00302

AC:

AN:

2650

East Asian (EAS)

AF:

0.00

AC:

AN:

3552

South Asian (SAS)

AF:

0.00

AC:

AN:

2681

European-Finnish (FIN)

AF:

0.000331

AC:

AN:

6044

Middle Eastern (MID)

AF:

0.00

AC:

AN:

215

European-Non Finnish (NFE)

AF:

0.000920

AC:

AN:

53274

Other (OTH)

AF:

0.00

AC:

AN:

1535

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.493

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00105

Hom.:

Bravo

AF:

0.000536

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000346

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000743

AC:

ExAC

AF:

0.000569

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Dec 01, 2022

CeGaT Center for Human Genetics Tuebingen

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

TSPAN6: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.58

BayesDel_noAF

Benign

-0.63

CADD

Benign

(source)

DANN

Uncertain

0.97

DEOGEN2

Benign

0.061

FATHMM_MKL

Benign

0.60

LIST_S2

Benign

0.72

M_CAP

Benign

0.020

MetaRNN

Benign

0.014

MetaSVM

Benign

-0.91

MutationAssessor

Benign

-2.2

PhyloP100

1.2

PrimateAI

Uncertain

0.51

PROVEAN

Benign

1.0

REVEL

Benign

0.25

Sift

Benign

0.34

Sift4G

Benign

0.83

Polyphen

0.0030

Vest4

0.041

MVP

0.62

MPC

0.051

ClinPred

0.022

GERP RS

3.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.13

gMVP

0.28

Mutation Taster

=98/2

polymorphism

(source)

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

Publications

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X-100635575-C-T

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over