11-44909757-C-T

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_130783.5(TSPAN18):​c.116C>T​(p.Thr39Ile) variant causes a missense change. The variant allele was found at a frequency of 0.000593 in 1,613,654 control chromosomes in the GnomAD database, including 9 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. T39T) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.0033 ( 6 hom., cov: 33)
Exomes 𝑓: 0.00031 ( 3 hom. )

Consequence

TSPAN18
NM_130783.5 missense

Scores

7
11

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 4.92
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 Benign. Variant got -16 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.009831578).
BP6
Variant 11-44909757-C-T is Benign according to our data. Variant chr11-44909757-C-T is described in ClinVar as [Benign]. Clinvar id is 713410.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS2
High Homozygotes in GnomAd4 at 6 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
TSPAN18NM_130783.5 linkuse as main transcriptc.116C>T p.Thr39Ile missense_variant 5/10 ENST00000520358.7

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
TSPAN18ENST00000520358.7 linkuse as main transcriptc.116C>T p.Thr39Ile missense_variant 5/105 NM_130783.5 P1

Frequencies

GnomAD3 genomes
AF:
0.00330
AC:
503
AN:
152220
Hom.:
6
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0117
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000589
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:
0.0000294
Gnomad OTH
AF:
0.00334
GnomAD3 exomes
AF:
0.000734
AC:
184
AN:
250748
Hom.:
2
AF XY:
0.000516
AC XY:
70
AN XY:
135650
show subpopulations
Gnomad AFR exome
AF:
0.0104
Gnomad AMR exome
AF:
0.000405
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:
0.00000881
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.000310
AC:
453
AN:
1461316
Hom.:
3
Cov.:
31
AF XY:
0.000267
AC XY:
194
AN XY:
727000
show subpopulations
Gnomad4 AFR exome
AF:
0.0118
Gnomad4 AMR exome
AF:
0.000403
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:
0.00000809
Gnomad4 OTH exome
AF:
0.000480
GnomAD4 genome
AF:
0.00331
AC:
504
AN:
152338
Hom.:
6
Cov.:
33
AF XY:
0.00306
AC XY:
228
AN XY:
74486
show subpopulations
Gnomad4 AFR
AF:
0.0117
Gnomad4 AMR
AF:
0.000588
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000294
Gnomad4 OTH
AF:
0.00331
Alfa
AF:
0.000575
Hom.:
1
Bravo
AF:
0.00384
ESP6500AA
AF:
0.0104
AC:
46
ESP6500EA
AF:
0.00
AC:
0
ExAC
AF:
0.000923
AC:
112
Asia WGS
AF:
0.000577
AC:
2
AN:
3478

ClinVar

Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not provided Benign:2
Benign, criteria provided, single submitternot providedBreakthrough Genomics, Breakthrough Genomics-- -
Benign, criteria provided, single submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpOct 09, 2017- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.23
BayesDel_addAF
Benign
-0.30
T
BayesDel_noAF
Benign
-0.19
CADD
Uncertain
24
DANN
Uncertain
1.0
DEOGEN2
Benign
0.17
.;.;T;.;T;.
Eigen
Uncertain
0.29
Eigen_PC
Uncertain
0.37
FATHMM_MKL
Uncertain
0.95
D
LIST_S2
Uncertain
0.94
D;D;D;D;.;D
MetaRNN
Benign
0.0098
T;T;T;T;T;T
MetaSVM
Benign
-0.31
T
MutationAssessor
Benign
1.9
.;.;L;.;L;.
MutationTaster
Benign
1.0
D;D
PrimateAI
Uncertain
0.61
T
PROVEAN
Benign
-1.6
N;N;N;N;N;N
REVEL
Uncertain
0.36
Sift
Benign
0.21
T;T;T;T;T;T
Sift4G
Benign
0.19
T;T;T;T;T;T
Polyphen
0.70
.;.;P;.;P;.
Vest4
0.80, 0.80
MVP
0.56
MPC
0.51
ClinPred
0.020
T
GERP RS
5.0
Varity_R
0.39
gMVP
0.57

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: rs34282417; hg19: chr11-44931308; API