Genetic Variant TMPRSS13:p.Ser259Leu (chr11-117913810-G-A) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001077263.3(TMPRSS13):c.776C>T(p.Ser259Leu) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,820 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

TMPRSS13
NM_001077263.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.85

Publications

0 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:

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ACMG classification

Classification was made for transcript

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

PM2

Very rare variant in population databases, with high coverage;

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.776C>T	p.Ser259Leu	missense	Exon 5 of 13	NP_001070731.1	Q9BYE2-6
TMPRSS13	NM_001244995.2		c.776C>T	p.Ser259Leu	missense	Exon 5 of 13	NP_001231924.1	Q9BYE2-2
TMPRSS13	NM_001206789.2		c.671C>T	p.Ser224Leu	missense	Exon 4 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.776C>T	p.Ser259Leu	missense	Exon 5 of 13	ENSP00000434279.1	Q9BYE2-6
TMPRSS13	ENST00000445164.6	TSL:1	c.776C>T	p.Ser259Leu	missense	Exon 5 of 12	ENSP00000394114.2	Q9BYE2-1
TMPRSS13	ENST00000430170.6	TSL:1	c.776C>T	p.Ser259Leu	missense	Exon 5 of 13	ENSP00000387702.2	Q9BYE2-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000401

AC:

AN:

249556

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000883

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461820

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727216

show subpopulations

African (AFR)

AF:

0.0000299

AC:

AN:

33474

American (AMR)

AF:

0.00

AC:

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26134

East Asian (EAS)

AF:

0.00

AC:

AN:

39698

South Asian (SAS)

AF:

0.00

AC:

AN:

86254

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53416

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5756

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1111978

Other (OTH)

AF:

0.00

AC:

AN:

60388

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome 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

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.51

BayesDel_addAF

Benign

0.011

BayesDel_noAF

Benign

-0.22

CADD

Pathogenic

(source)

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.034

Eigen

Pathogenic

0.80

Eigen_PC

Pathogenic

0.77

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.96

M_CAP

Uncertain

0.090

MetaRNN

Uncertain

0.53

MetaSVM

Uncertain

-0.056

MutationAssessor

Uncertain

2.6

PhyloP100

6.8

PrimateAI

Benign

0.38

PROVEAN

Uncertain

-3.5

REVEL

Uncertain

0.41

Sift

Uncertain

0.0060

Sift4G

Benign

0.067

Polyphen

0.98

Vest4

0.60

MutPred

0.49

Loss of disorder (P = 0.0087)

MVP

0.89

MPC

0.74

ClinPred

0.98

GERP RS

5.7

gMVP

0.76

Mutation Taster

=61/39

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.21

Details are displayed if max score is > 0.2

DS_DL_spliceai

0.21

Position offset: -33

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over