11-117904080-C-T

Variant summary

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

The NM_001077263.3(TMPRSS13):​c.1403G>A​(p.Arg468Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000695 in 1,614,042 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).

Frequency

Genomes: 𝑓 0.00051 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00071 ( 1 hom. )

Consequence

TMPRSS13
NM_001077263.3 missense

Scores

1
2
16

Clinical Significance

Uncertain significance criteria provided, multiple submitters, no conflicts U:2

Conservation

PhyloP100: 1.41
Variant links:
Genes affected
TMPRSS13 (HGNC:29808): (transmembrane serine protease 13) This gene encodes a member of the type II transmembrane serine protease family. The encoded protein contains a type II transmembrane domain, a receptor class A domain, a scavenger receptor cysteine-rich domain and a protease domain. Transmembrane serine proteases are regulated by protease inhibitors and known to function in development, homeostasis, infection, and tumorigenesis. This protein facilitates entry of viruses into host cells by proteolytically cleaving and activating viral envelope glycoproteins. [provided by RefSeq, Aug 2021]

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 rank MANE Protein UniProt
TMPRSS13NM_001077263.3 linkc.1403G>A p.Arg468Gln missense_variant Exon 11 of 13 ENST00000524993.6 NP_001070731.1 Q9BYE2-6
TMPRSS13NM_001244995.2 linkc.1403G>A p.Arg468Gln missense_variant Exon 11 of 13 NP_001231924.1 Q9BYE2-2
TMPRSS13NM_001206789.2 linkc.1298G>A p.Arg433Gln missense_variant Exon 10 of 12 NP_001193718.1 Q9BYE2-3

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
TMPRSS13ENST00000524993.6 linkc.1403G>A p.Arg468Gln missense_variant Exon 11 of 13 1 NM_001077263.3 ENSP00000434279.1 Q9BYE2-6
TMPRSS13ENST00000445164.6 linkc.1403G>A p.Arg468Gln missense_variant Exon 11 of 12 1 ENSP00000394114.2 Q9BYE2-1
TMPRSS13ENST00000430170.6 linkc.1403G>A p.Arg468Gln missense_variant Exon 11 of 13 1 ENSP00000387702.2 Q9BYE2-2
TMPRSS13ENST00000528626.5 linkc.1298G>A p.Arg433Gln missense_variant Exon 10 of 12 1 ENSP00000435813.1 Q9BYE2-3

Frequencies

GnomAD3 genomes
AF:
0.000506
AC:
77
AN:
152194
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.000265
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000654
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000207
Gnomad FIN
AF:
0.00160
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000691
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.000698
AC:
174
AN:
249126
Hom.:
0
AF XY:
0.000651
AC XY:
88
AN XY:
135142
show subpopulations
Gnomad AFR exome
AF:
0.000258
Gnomad AMR exome
AF:
0.0000871
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.000426
Gnomad FIN exome
AF:
0.00279
Gnomad NFE exome
AF:
0.000813
Gnomad OTH exome
AF:
0.000331
GnomAD4 exome
AF:
0.000714
AC:
1044
AN:
1461730
Hom.:
1
Cov.:
36
AF XY:
0.000692
AC XY:
503
AN XY:
727164
show subpopulations
Gnomad4 AFR exome
AF:
0.0000597
Gnomad4 AMR exome
AF:
0.0000671
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.000325
Gnomad4 FIN exome
AF:
0.00219
Gnomad4 NFE exome
AF:
0.000785
Gnomad4 OTH exome
AF:
0.000348
GnomAD4 genome
AF:
0.000506
AC:
77
AN:
152312
Hom.:
0
Cov.:
32
AF XY:
0.000510
AC XY:
38
AN XY:
74482
show subpopulations
Gnomad4 AFR
AF:
0.000265
Gnomad4 AMR
AF:
0.0000653
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000207
Gnomad4 FIN
AF:
0.00160
Gnomad4 NFE
AF:
0.000691
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000417
Hom.:
0
Bravo
AF:
0.000348
TwinsUK
AF:
0.000809
AC:
3
ALSPAC
AF:
0.000259
AC:
1
ESP6500AA
AF:
0.000739
AC:
3
ESP6500EA
AF:
0.000240
AC:
2
ExAC
AF:
0.000678
AC:
82
Asia WGS
AF:
0.000289
AC:
1
AN:
3478
EpiCase
AF:
0.000763
EpiControl
AF:
0.000830

ClinVar

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

Submissions by phenotype

not provided Uncertain:2
-
Breakthrough Genomics, Breakthrough Genomics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: not provided

- -

Jun 28, 2020
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.18
BayesDel_addAF
Benign
-0.33
T
BayesDel_noAF
Benign
-0.33
CADD
Pathogenic
35
DANN
Pathogenic
1.0
DEOGEN2
Benign
0.18
.;T;.;T
Eigen
Benign
0.062
Eigen_PC
Benign
0.20
FATHMM_MKL
Uncertain
0.94
D
LIST_S2
Uncertain
0.89
D;D;D;D
M_CAP
Benign
0.027
D
MetaRNN
Benign
0.017
T;T;T;T
MetaSVM
Benign
-0.72
T
MutationAssessor
Benign
-0.17
.;.;N;.
PrimateAI
Benign
0.39
T
PROVEAN
Benign
-1.0
N;N;N;N
REVEL
Benign
0.19
Sift
Benign
0.32
T;T;T;T
Sift4G
Benign
0.25
T;T;T;T
Polyphen
1.0
.;D;.;.
Vest4
0.23
MVP
0.70
MPC
0.29
ClinPred
0.024
T
GERP RS
5.0
gMVP
0.75

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.86
Details are displayed if max score is > 0.2
DS_AG_spliceai
0.86
Position offset: -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: rs200481694; hg19: chr11-117774795; API