Variant 11-117914449-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001077263.3(TMPRSS13):c.622G>A(p.Ala208Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000547 in 1,461,830 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000055 ( 0 hom. )

Consequence

TMPRSS13
NM_001077263.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.298

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 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.13007563).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TMPRSS13	NM_001077263.3 linkuse as main transcript	c.622G>A	p.Ala208Thr	missense_variant	4/13	ENST00000524993.6	NP_001070731.1	Q9BYE2-6
TMPRSS13	NM_001244995.2 linkuse as main transcript	c.622G>A	p.Ala208Thr	missense_variant	4/13		NP_001231924.1	Q9BYE2-2
TMPRSS13	NM_001206789.2 linkuse as main transcript	c.517G>A	p.Ala173Thr	missense_variant	3/12		NP_001193718.1	Q9BYE2-3
TMPRSS13	NM_001206790.2 linkuse as main transcript	c.622G>A	p.Ala208Thr	missense_variant	4/9		NP_001193719.1	Q9BYE2-4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TMPRSS13	ENST00000524993.6 linkuse as main transcript	c.622G>A	p.Ala208Thr	missense_variant	4/13	1	NM_001077263.3	ENSP00000434279.1		Q9BYE2-6

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000401

AC:

AN:

249550

Hom.:

AF XY:

0.00000739

AC XY:

AN XY:

135382

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000290

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000547

AC:

AN:

1461830

Hom.:

Cov.:

AF XY:

0.00000413

AC XY:

AN XY:

727220

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000224

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:

0.00000629

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.0000113

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 20, 2023

The c.622G>A (p.A208T) alteration is located in exon 4 (coding exon 4) of the TMPRSS13 gene. This alteration results from a G to A substitution at nucleotide position 622, causing the alanine (A) at amino acid position 208 to be replaced by a threonine (T). 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

Benign

0.085

BayesDel_addAF

Benign

-0.090

BayesDel_noAF

Benign

-0.37

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.0083

.;T;.;T;.

Eigen

Benign

-0.71

Eigen_PC

Benign

-0.74

FATHMM_MKL

Benign

0.036

LIST_S2

Benign

0.79

T;T;T;T;T

M_CAP

Uncertain

0.11

MetaRNN

Benign

0.13

T;T;T;T;T

MetaSVM

Benign

-0.52

MutationAssessor

Benign

0.88

.;.;L;.;L

PrimateAI

Benign

0.35

PROVEAN

Benign

-0.59

N;N;N;N;N

REVEL

Benign

0.12

Sift

Benign

0.41

T;T;T;T;T

Sift4G

Benign

0.43

T;T;T;T;T

Polyphen

0.093

.;B;.;.;.

Vest4

0.31

MutPred

0.31

.;Loss of catalytic residue at A208 (P = 0.0151);Loss of catalytic residue at A208 (P = 0.0151);Loss of catalytic residue at A208 (P = 0.0151);Loss of catalytic residue at A208 (P = 0.0151);

MVP

0.86

MPC

0.24

ClinPred

0.15

GERP RS

-0.49

gMVP

0.24

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.

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