Variant X-100633968-T-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_003270.4(TSPAN6):c.413A>T(p.Asp138Val) variant causes a missense change. The variant allele was found at a frequency of 0.000000915 in 1,093,387 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 1 hemizygotes in GnomAD. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 21)

Exomes 𝑓: 9.1e-7 ( 0 hom. 1 hem. )

Consequence

TSPAN6
NM_003270.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.59

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 made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.76

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TSPAN6	NM_003270.4 linkuse as main transcript	c.413A>T	p.Asp138Val	missense_variant	4/8	ENST00000373020.9	NP_003261.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
TSPAN6	ENST00000373020.9 linkuse as main transcript	c.413A>T	p.Asp138Val	missense_variant	4/8	1	NM_003270.4	ENSP00000362111	P1
TSPAN6	ENST00000612152.4 linkuse as main transcript	c.149A>T	p.Asp50Val	missense_variant	4/7	5		ENSP00000482130
TSPAN6	ENST00000494424.1 linkuse as main transcript	n.685A>T		non_coding_transcript_exon_variant	5/6	2
TSPAN6	ENST00000496771.5 linkuse as main transcript	n.825A>T		non_coding_transcript_exon_variant	4/6	3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

9.15e-7

AC:

AN:

1093387

Hom.:

Cov.:

AF XY:

0.00000278

AC XY:

AN XY:

359145

show subpopulations

Gnomad4 AFR exome

AF:

0.0000380

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 08, 2022

The c.413A>T (p.D138V) alteration is located in exon 4 (coding exon 4) of the TSPAN6 gene. This alteration results from a A to T substitution at nucleotide position 413, causing the aspartic acid (D) at amino acid position 138 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.50

BayesDel_addAF

Pathogenic

0.44

BayesDel_noAF

Pathogenic

0.39

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.34

.;T;T

FATHMM_MKL

Uncertain

0.96

LIST_S2

Benign

0.83

T;T;T

M_CAP

Pathogenic

0.37

MetaRNN

Pathogenic

0.76

D;D;D

MetaSVM

Uncertain

-0.11

MutationAssessor

Uncertain

2.6

.;M;.

MutationTaster

Benign

1.0

PrimateAI

Benign

0.41

PROVEAN

Pathogenic

-4.8

.;D;.

REVEL

Pathogenic

0.70

Sift

Uncertain

0.0020

.;D;.

Sift4G

Uncertain

0.028

D;D;D

Polyphen

0.17

.;B;.

Vest4

0.28

MutPred

0.54

.;Loss of disorder (P = 0.0112);.;

MVP

0.93

MPC

0.11

ClinPred

0.99

GERP RS

5.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.75

gMVP

0.85

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over