Genetic Variant NM_003270.4:c.510A>G (chrX-100633480-T-C) – ACMG Classification: Benign (-11 pts)

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_003270.4(TSPAN6):c.510A>G(p.Glu170Glu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000473 in 1,205,859 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 16 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00026 ( 0 hom., 9 hem., cov: 22)

Exomes 𝑓: 0.000026 ( 0 hom. 7 hem. )

Consequence

TSPAN6
NM_003270.4 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.629

Publications

0 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 -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BP6

Variant X-100633480-T-C is Benign according to our data. Variant chrX-100633480-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 2661033.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-0.629 with no splicing effect.

BS2

High Hemizygotes in GnomAd4 at 9 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TSPAN6	NM_003270.4 link	c.510A>G	p.Glu170Glu	synonymous_variant	Exon 5 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.510A>G	p.Glu170Glu	synonymous_variant	Exon 5 of 8	1	NM_003270.4	ENSP00000362111.4	O43657
TSPAN6	ENST00000612152.4 link	c.246A>G	p.Glu82Glu	synonymous_variant	Exon 5 of 7	5		ENSP00000482130.1	A0A087WYV6
TSPAN6	ENST00000494424.1 link	n.782A>G		non_coding_transcript_exon_variant	Exon 6 of 6	2
TSPAN6	ENST00000496771.5 link	n.922A>G		non_coding_transcript_exon_variant	Exon 5 of 6	3

Frequencies

GnomAD3 genomes

AF:

0.000259

AC:

AN:

111764

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000813

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000190

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000557

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000719

AC:

AN:

180836

AF XY:

0.0000153

show subpopulations

Gnomad AFR exome

AF:

0.000764

Gnomad AMR exome

AF:

0.0000741

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000733

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000256

AC:

AN:

1094042

Hom.:

Cov.:

AF XY:

0.0000195

AC XY:

AN XY:

359510

show subpopulations

African (AFR)

AF:

0.000456

AC:

AN:

26307

American (AMR)

AF:

0.0000856

AC:

AN:

35048

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19322

East Asian (EAS)

AF:

0.000298

AC:

AN:

30170

South Asian (SAS)

AF:

0.00

AC:

AN:

53726

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40499

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4118

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

838891

Other (OTH)

AF:

0.0000870

AC:

AN:

45961

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.487

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.000259

AC:

AN:

111817

Hom.:

Cov.:

AF XY:

0.000265

AC XY:

AN XY:

34015

show subpopulations

African (AFR)

AF:

0.000811

AC:

AN:

30822

American (AMR)

AF:

0.000190

AC:

AN:

10524

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2645

East Asian (EAS)

AF:

0.000559

AC:

AN:

3578

South Asian (SAS)

AF:

0.00

AC:

AN:

2589

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6062

Middle Eastern (MID)

AF:

0.00

AC:

AN:

218

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

53162

Other (OTH)

AF:

0.00

AC:

AN:

1531

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.518

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.000427

Hom.:

Bravo

AF:

0.000287

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Sep 01, 2022

CeGaT Center for Human Genetics Tuebingen

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

TSPAN6: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

7.3

(source)

DANN

Benign

0.59

PhyloP100

-0.63

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Mutation Taster

=100/0

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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NM_003270.4:c.510A>G

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