dbSNP rs189159745: TSPAN6:p.Gln132His (chrX-100633985-C-G) – 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.396G>C(p.Gln132His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. Q132Q) has been classified as Benign.

Frequency

Genomes: not found (cov: 21)

Consequence

TSPAN6
NM_003270.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.86

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=0.076006085).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TSPAN6	NM_003270.4 link	c.396G>C	p.Gln132His	missense_variant	Exon 4 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.396G>C	p.Gln132His	missense_variant	Exon 4 of 8	1	NM_003270.4	ENSP00000362111.4	O43657
TSPAN6	ENST00000612152.4 link	c.132G>C	p.Gln44His	missense_variant	Exon 4 of 7	5		ENSP00000482130.1	A0A087WYV6
TSPAN6	ENST00000494424.1 link	n.668G>C		non_coding_transcript_exon_variant	Exon 5 of 6	2
TSPAN6	ENST00000496771.5 link	n.808G>C		non_coding_transcript_exon_variant	Exon 4 of 6	3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

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

Benign

0.23

BayesDel_addAF

Benign

-0.26

BayesDel_noAF

Benign

-0.62

CADD

Benign

1.4

(source)

DANN

Benign

0.86

DEOGEN2

Benign

0.094

.;T;T

FATHMM_MKL

Benign

0.023

LIST_S2

Benign

0.73

T;T;T

M_CAP

Benign

0.039

MetaRNN

Benign

0.076

T;T;T

MetaSVM

Benign

-0.82

MutationAssessor

Benign

0.29

.;N;.

PhyloP100

-1.9

PrimateAI

Benign

0.38

PROVEAN

Benign

-0.73

.;N;.

REVEL

Benign

0.13

Sift

Benign

0.083

.;T;.

Sift4G

Benign

0.13

T;T;T

Polyphen

0.0

.;B;.

Vest4

0.15

MutPred

0.30

.;Loss of ubiquitination at K131 (P = 0.0982);.;

MVP

0.57

MPC

0.050

ClinPred

0.031

GERP RS

-5.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.23

gMVP

0.57

Mutation Taster

=83/17

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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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