Variant chr11-44909729-A-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_130783.5(TSPAN18):c.88A>T(p.Ile30Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000113 in 1,612,188 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00033 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000090 ( 1 hom. )

Consequence

TSPAN18
NM_130783.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.180

Variant links:

Genes affected

TSPAN18 (HGNC:20660): (tetraspanin 18) Predicted to be integral component of membrane. Predicted to be integral component of plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

TSPAN18 links:

TP53I11 (HGNC:16842): (tumor protein p53 inducible protein 11) Predicted to be involved in negative regulation of cell population proliferation. Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

TP53I11 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.08259407).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TSPAN18	NM_130783.5 linkuse as main transcript	c.88A>T	p.Ile30Phe	missense_variant	5/10	ENST00000520358.7	NP_570139.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TSPAN18	ENST00000520358.7 linkuse as main transcript	c.88A>T	p.Ile30Phe	missense_variant	5/10	5	NM_130783.5	ENSP00000429993	P1

Frequencies

GnomAD3 genomes

AF:

0.000335

AC:

AN:

152126

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000966

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000393

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:

0.0000735

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000132

AC:

AN:

249742

Hom.:

AF XY:

0.000111

AC XY:

AN XY:

135200

show subpopulations

Gnomad AFR exome

AF:

0.00112

Gnomad AMR exome

AF:

0.000116

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000882

Gnomad OTH exome

AF:

0.000164

GnomAD4 exome

AF:

0.0000897

AC:

131

AN:

1459944

Hom.:

Cov.:

AF XY:

0.0000936

AC XY:

AN XY:

726326

show subpopulations

Gnomad4 AFR exome

AF:

0.00108

Gnomad4 AMR exome

AF:

0.000179

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:

0.0000648

Gnomad4 OTH exome

AF:

0.000182

GnomAD4 genome

AF:

0.000335

AC:

AN:

152244

Hom.:

Cov.:

AF XY:

0.000376

AC XY:

AN XY:

74438

show subpopulations

Gnomad4 AFR

AF:

0.000963

Gnomad4 AMR

AF:

0.000392

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000735

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000597

Hom.:

Bravo

AF:

0.000502

ESP6500AA

AF:

0.00159

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000132

AC:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.000178

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

Sep 27, 2022

The c.88A>T (p.I30F) alteration is located in exon 4 (coding exon 2) of the TSPAN18 gene. This alteration results from a A to T substitution at nucleotide position 88, causing the isoleucine (I) at amino acid position 30 to be replaced by a phenylalanine (F). 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

Benign

0.21

BayesDel_addAF

Benign

-0.29

BayesDel_noAF

Benign

-0.24

CADD

Benign

8.6

DANN

Benign

0.96

DEOGEN2

Benign

0.34

.;.;T;.;T;.

Eigen

Benign

-0.97

Eigen_PC

Benign

-0.95

FATHMM_MKL

Benign

0.30

LIST_S2

Uncertain

0.89

D;D;D;D;.;D

M_CAP

Benign

0.083

MetaRNN

Benign

0.083

T;T;T;T;T;T

MetaSVM

Benign

-0.90

MutationAssessor

Benign

0.28

.;.;N;.;N;.

MutationTaster

Benign

0.93

D;D

PrimateAI

Benign

0.33

PROVEAN

Uncertain

-3.7

D;D;D;D;D;D

REVEL

Uncertain

0.35

Sift

Uncertain

0.0040

D;D;D;D;D;D

Sift4G

Uncertain

0.0050

D;T;D;D;D;D

Polyphen

0.087

.;.;B;.;B;.

Vest4

0.50

MVP

0.18

MPC

0.52

ClinPred

0.080

GERP RS

-5.2

Varity_R

0.30

gMVP

0.66

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over