Variant 11-117914509-A-G details in Genebe, Genetics Data Aggregator

Variant summary

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

The ENST00000524993.6(TMPRSS13):c.562T>C(p.Phe188Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00000434 in 1,613,782 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: 32)

Exomes 𝑓: 0.0000041 ( 0 hom. )

Consequence

TMPRSS13
ENST00000524993.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.59

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 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
TMPRSS13	NM_001077263.3 linkuse as main transcript	c.562T>C	p.Phe188Leu	missense_variant	4/13	ENST00000524993.6	NP_001070731.1
TMPRSS13	NM_001244995.2 linkuse as main transcript	c.562T>C	p.Phe188Leu	missense_variant	4/13		NP_001231924.1
TMPRSS13	NM_001206789.2 linkuse as main transcript	c.457T>C	p.Phe153Leu	missense_variant	3/12		NP_001193718.1
TMPRSS13	NM_001206790.2 linkuse as main transcript	c.562T>C	p.Phe188Leu	missense_variant	4/9		NP_001193719.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TMPRSS13	ENST00000524993.6 linkuse as main transcript	c.562T>C	p.Phe188Leu	missense_variant	4/13	1	NM_001077263.3	ENSP00000434279	A2	Q9BYE2-6

Frequencies

GnomAD3 genomes

AF:

0.00000658

AC:

AN:

152070

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

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:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000120

AC:

AN:

249298

Hom.:

AF XY:

0.0000148

AC XY:

AN XY:

135256

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 SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000265

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000410

AC:

AN:

1461712

Hom.:

Cov.:

AF XY:

0.00000688

AC XY:

AN XY:

727178

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000450

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.00000658

AC:

AN:

152070

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74270

show subpopulations

Gnomad4 AFR

AF:

0.00

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:

0.0000147

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000488

Hom.:

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 submitter

clinical testing

Ambry Genetics

Dec 27, 2023

The c.562T>C (p.F188L) alteration is located in exon 4 (coding exon 4) of the TMPRSS13 gene. This alteration results from a T to C substitution at nucleotide position 562, causing the phenylalanine (F) at amino acid position 188 to be replaced by a leucine (L). 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

Pathogenic

0.72

BayesDel_addAF

Uncertain

0.14

BayesDel_noAF

Uncertain

-0.030

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.030

.;T;.;T;.

Eigen

Uncertain

0.50

Eigen_PC

Uncertain

0.47

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Benign

0.39

T;T;T;T;T

M_CAP

Uncertain

0.19

MetaRNN

Uncertain

0.73

D;D;D;D;D

MetaSVM

Uncertain

0.46

MutationAssessor

Uncertain

2.3

.;.;M;.;M

MutationTaster

Benign

1.0

D;D;D;D;D

PrimateAI

Uncertain

0.69

PROVEAN

Benign

-1.0

N;N;N;N;D

REVEL

Uncertain

0.50

Sift

Benign

0.059

T;T;T;T;D

Sift4G

Benign

0.46

T;T;T;T;D

Polyphen

1.0

.;D;.;.;.

Vest4

0.72

MutPred

0.36

.;Loss of loop (P = 0.1242);Loss of loop (P = 0.1242);Loss of loop (P = 0.1242);Loss of loop (P = 0.1242);

MVP

0.96

MPC

0.91

ClinPred

0.90

GERP RS

5.8

gMVP

0.46

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.10

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over