Genetic Variant NM_001077263.3:c.1403G>A (chr11-117904080-C-T) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PP3_Moderate

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. 14/23 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

Clinical Significance

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

Conservation

PhyloP100: 1.41

Publications

2 publications found

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]

TMPRSS13 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PP3

Splicing predictors support a deleterious effect. Scorers claiming Pathogenic: max_spliceai. No scorers claiming Uncertain. No scorers claiming Benign.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001077263.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TMPRSS13	NM_001077263.3	MANE Select	c.1403G>A	p.Arg468Gln	missense	Exon 11 of 13	NP_001070731.1	Q9BYE2-6
TMPRSS13	NM_001244995.2		c.1403G>A	p.Arg468Gln	missense	Exon 11 of 13	NP_001231924.1	Q9BYE2-2
TMPRSS13	NM_001206789.2		c.1298G>A	p.Arg433Gln	missense	Exon 10 of 12	NP_001193718.1	Q9BYE2-3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TMPRSS13	ENST00000524993.6	TSL:1 MANE Select	c.1403G>A	p.Arg468Gln	missense	Exon 11 of 13	ENSP00000434279.1	Q9BYE2-6
TMPRSS13	ENST00000445164.6	TSL:1	c.1403G>A	p.Arg468Gln	missense	Exon 11 of 12	ENSP00000394114.2	Q9BYE2-1
TMPRSS13	ENST00000430170.6	TSL:1	c.1403G>A	p.Arg468Gln	missense	Exon 11 of 13	ENSP00000387702.2	Q9BYE2-2

Frequencies

GnomAD3 genomes

AF:

0.000506

AC:

AN:

152194

Hom.:

Cov.:

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

GnomAD2 exomes

AF:

0.000698

AC:

174

AN:

249126

AF XY:

0.000651

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 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.:

Cov.:

AF XY:

0.000692

AC XY:

503

AN XY:

727164

show subpopulations

African (AFR)

AF:

0.0000597

AC:

AN:

33480

American (AMR)

AF:

0.0000671

AC:

AN:

44704

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26124

East Asian (EAS)

AF:

0.00

AC:

AN:

39698

South Asian (SAS)

AF:

0.000325

AC:

AN:

86206

European-Finnish (FIN)

AF:

0.00219

AC:

117

AN:

53416

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.000785

AC:

873

AN:

1111948

Other (OTH)

AF:

0.000348

AC:

AN:

60386

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.485

Heterozygous variant carriers

123

184

246

307

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

108

144

180

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000506

AC:

AN:

152312

Hom.:

Cov.:

AF XY:

0.000510

AC XY:

AN XY:

74482

show subpopulations

African (AFR)

AF:

0.000265

AC:

AN:

41564

American (AMR)

AF:

0.0000653

AC:

AN:

15312

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5182

South Asian (SAS)

AF:

0.000207

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00160

AC:

AN:

10626

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000691

AC:

AN:

68012

Other (OTH)

AF:

0.00

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.487

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000412

Hom.:

Bravo

AF:

0.000348

TwinsUK

AF:

0.000809

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.000739

AC:

ESP6500EA

AF:

0.000240

AC:

ExAC

AF:

0.000678

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.000763

EpiControl

AF:

0.000830

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.18

BayesDel_addAF

Benign

-0.33

BayesDel_noAF

Benign

-0.33

CADD

Pathogenic

(source)

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.18

Eigen

Benign

0.062

Eigen_PC

Benign

0.20

FATHMM_MKL

Uncertain

0.94

LIST_S2

Uncertain

0.89

M_CAP

Benign

0.027

MetaRNN

Benign

0.017

MetaSVM

Benign

-0.72

MutationAssessor

Benign

-0.17

PhyloP100

1.4

PrimateAI

Benign

0.39

PROVEAN

Benign

-1.0

REVEL

Benign

0.19

Sift

Benign

0.32

Sift4G

Benign

0.25

Polyphen

1.0

Vest4

0.23

MVP

0.70

MPC

0.29

ClinPred

0.024

GERP RS

5.0

gMVP

0.75

Mutation Taster

=85/15

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over