Variant 12-30982631-A-G details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_001370302.1(TSPAN11):c.556A>G(p.Lys186Glu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,012 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 35)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

TSPAN11
NM_001370302.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 9.00

Variant links:

Genes affected

TSPAN11 (HGNC:30795): (tetraspanin 11) Predicted to be involved in cell migration. Predicted to be integral component of membrane. Predicted to be integral component of plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

TSPAN11 links:

TSPAN11-AS1 (HGNC:56687): (TSPAN11 antisense RNA 1)

TSPAN11-AS1 links:

Genome browser will be placed here

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, 0.778

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TSPAN11	NM_001370302.1 linkuse as main transcript	c.556A>G	p.Lys186Glu	missense_variant	6/8	ENST00000546076.6
TSPAN11-AS1	XR_007063261.1 linkuse as main transcript	n.295-3956T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
TSPAN11	ENST00000546076.6 linkuse as main transcript	c.556A>G	p.Lys186Glu	missense_variant	6/8	2	NM_001370302.1	P1
TSPAN11	ENST00000261177.10 linkuse as main transcript	c.556A>G	p.Lys186Glu	missense_variant	6/8	1		P1
TSPAN11-AS1	ENST00000613860.4 linkuse as main transcript	n.508-3956T>C		intron_variant, non_coding_transcript_variant		5
TSPAN11	ENST00000535215.5 linkuse as main transcript	c.343A>G	p.Lys115Glu	missense_variant	5/7	2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.85e-7

AC:

AN:

1460012

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

726286

show subpopulations

Gnomad4 AFR exome

AF:

0.00

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:

9.00e-7

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 02, 2021

The c.556A>G (p.K186E) alteration is located in exon 6 (coding exon 5) of the TSPAN11 gene. This alteration results from a A to G substitution at nucleotide position 556, causing the lysine (K) at amino acid position 186 to be replaced by a glutamic acid (E). 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

Pathogenic

0.84

BayesDel_addAF

Pathogenic

0.28

BayesDel_noAF

Pathogenic

0.16

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.34

T;.;T

Eigen

Uncertain

0.40

Eigen_PC

Uncertain

0.32

FATHMM_MKL

Pathogenic

0.98

M_CAP

Benign

0.032

MetaRNN

Pathogenic

0.78

D;D;D

MetaSVM

Uncertain

0.26

MutationAssessor

Uncertain

2.7

M;.;M

MutationTaster

Benign

1.0

D;D;D;D

PrimateAI

Uncertain

0.75

PROVEAN

Uncertain

-3.1

D;D;D

REVEL

Pathogenic

0.68

Sift

Uncertain

0.0060

D;D;D

Sift4G

Uncertain

0.014

D;D;D

Polyphen

1.0

D;.;D

Vest4

0.82

MutPred

0.57

Loss of methylation at K186 (P = 0.0015);.;Loss of methylation at K186 (P = 0.0015);

MVP

0.55

MPC

0.51

ClinPred

0.95

GERP RS

4.0

Varity_R

0.72

gMVP

0.83

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