chr11-44926750-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_130783.5(TSPAN18):​c.692C>T​(p.Ala231Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000372 in 1,614,014 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)
Exomes 𝑓: 0.0000034 ( 0 hom. )

Consequence

TSPAN18
NM_130783.5 missense

Scores

6
13

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.28
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]
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
TSPAN18NM_130783.5 linkuse as main transcriptc.692C>T p.Ala231Val missense_variant 9/10 ENST00000520358.7 NP_570139.3

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
TSPAN18ENST00000520358.7 linkuse as main transcriptc.692C>T p.Ala231Val missense_variant 9/105 NM_130783.5 ENSP00000429993 P1

Frequencies

GnomAD3 genomes
AF:
0.00000657
AC:
1
AN:
152212
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0000241
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
GnomAD3 exomes
AF:
0.0000119
AC:
3
AN:
251416
Hom.:
0
AF XY:
0.00000736
AC XY:
1
AN XY:
135888
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.000163
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000342
AC:
5
AN:
1461802
Hom.:
0
Cov.:
30
AF XY:
0.00000275
AC XY:
2
AN XY:
727218
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000252
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000270
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
AF:
0.00000657
AC:
1
AN:
152212
Hom.:
0
Cov.:
33
AF XY:
0.00
AC XY:
0
AN XY:
74364
show subpopulations
Gnomad4 AFR
AF:
0.0000241
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.00000756
ExAC
AF:
0.00000824
AC:
1

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 submitterclinical testingAmbry GeneticsJul 20, 2021The c.692C>T (p.A231V) alteration is located in exon 8 (coding exon 6) of the TSPAN18 gene. This alteration results from a C to T substitution at nucleotide position 692, causing the alanine (A) at amino acid position 231 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
Benign
0.15
BayesDel_addAF
Benign
-0.16
T
BayesDel_noAF
Benign
-0.24
CADD
Benign
22
DANN
Uncertain
0.98
DEOGEN2
Benign
0.084
T;T
Eigen
Benign
-0.20
Eigen_PC
Benign
-0.060
FATHMM_MKL
Uncertain
0.96
D
LIST_S2
Uncertain
0.95
D;.
M_CAP
Benign
0.051
D
MetaRNN
Uncertain
0.69
D;D
MetaSVM
Benign
-0.69
T
MutationAssessor
Benign
0.10
N;N
MutationTaster
Benign
1.0
D;D
PrimateAI
Uncertain
0.72
T
PROVEAN
Benign
-0.47
N;N
REVEL
Uncertain
0.33
Sift
Benign
1.0
T;T
Sift4G
Benign
0.28
T;T
Polyphen
0.099
B;B
Vest4
0.69
MutPred
0.70
Gain of stability (P = 0.0432);Gain of stability (P = 0.0432);
MVP
0.62
MPC
0.33
ClinPred
0.33
T
GERP RS
4.4
Varity_R
0.11
gMVP
0.61

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.

Other links and lift over

dbSNP: rs756112106; hg19: chr11-44948301; API