Genetic Variant NM_003270.4:c.17G>A (chrX-100636678-C-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_003270.4(TSPAN6):c.17G>A(p.Arg6Gln) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. 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. R6P) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0 ( 0 hom., 0 hem., cov: 23)

Failed GnomAD Quality Control

Consequence

TSPAN6
NM_003270.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.69

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:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.13653824).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TSPAN6	NM_003270.4 link	c.17G>A	p.Arg6Gln	missense_variant	Exon 1 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.17G>A	p.Arg6Gln	missense_variant	Exon 1 of 8	1	NM_003270.4	ENSP00000362111.4	O43657
TSPAN6	ENST00000496771.5 link	n.12G>A		non_coding_transcript_exon_variant	Exon 1 of 6	3
TSPAN6	ENST00000612152.4 link	c.-178+115G>A		intron_variant	Intron 1 of 6	5		ENSP00000482130.1	A0A087WYV6
TSPAN6	ENST00000494424.1 link	n.359+115G>A		intron_variant	Intron 2 of 5	2

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

111820

Hom.:

Cov.:

Gnomad AFR

AF:

0.00

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

111820

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

33972

African (AFR)

AF:

0.00

AC:

AN:

30742

American (AMR)

AF:

0.00

AC:

AN:

10607

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2649

East Asian (EAS)

AF:

0.00

AC:

AN:

3558

South Asian (SAS)

AF:

0.00

AC:

AN:

2609

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6098

Middle Eastern (MID)

AF:

0.00

AC:

AN:

238

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

53130

Other (OTH)

AF:

0.00

AC:

AN:

1509

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.35

BayesDel_addAF

Benign

-0.30

BayesDel_noAF

Benign

-0.67

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.015

FATHMM_MKL

Uncertain

0.84

LIST_S2

Uncertain

0.88

M_CAP

Benign

0.019

MetaRNN

Benign

0.14

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.8

PhyloP100

3.7

PrimateAI

Uncertain

0.56

PROVEAN

Benign

-1.4

REVEL

Benign

0.025

Sift

Benign

0.033

Sift4G

Uncertain

0.031

Polyphen

0.017

Vest4

0.35

MutPred

0.21

Gain of relative solvent accessibility (P = 0.0479);

MVP

0.092

MPC

0.060

ClinPred

0.85

GERP RS

3.5

PromoterAI

-0.15

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.24

gMVP

0.58

Mutation Taster

=86/14

polymorphism

(source)

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over