Variant 11-117905728-G-A details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_001077263.3(TMPRSS13):c.1291C>T(p.His431Tyr) variant causes a missense change. The variant allele was found at a frequency of 0.000000692 in 1,445,916 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

TMPRSS13
NM_001077263.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.11

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	UniProt
TMPRSS13	NM_001077263.3 link	c.1291C>T	p.His431Tyr	missense_variant	10/13	ENST00000524993.6	NP_001070731.1	Q9BYE2-6
TMPRSS13	NM_001244995.2 link	c.1291C>T	p.His431Tyr	missense_variant	10/13		NP_001231924.1	Q9BYE2-2
TMPRSS13	NM_001206789.2 link	c.1186C>T	p.His396Tyr	missense_variant	9/12		NP_001193718.1	Q9BYE2-3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
TMPRSS13	ENST00000524993.6 link	c.1291C>T	p.His431Tyr	missense_variant	10/13	1	NM_001077263.3	ENSP00000434279.1	Q9BYE2-6
TMPRSS13	ENST00000445164.6 link	c.1291C>T	p.His431Tyr	missense_variant	10/12	1		ENSP00000394114.2	Q9BYE2-1
TMPRSS13	ENST00000430170.6 link	c.1291C>T	p.His431Tyr	missense_variant	10/13	1		ENSP00000387702.2	Q9BYE2-2
TMPRSS13	ENST00000528626.5 link	c.1186C>T	p.His396Tyr	missense_variant	9/12	1		ENSP00000435813.1	Q9BYE2-3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000437

AC:

AN:

228584

Hom.:

AF XY:

0.00000811

AC XY:

AN XY:

123272

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:

0.00000980

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.92e-7

AC:

AN:

1445916

Hom.:

Cov.:

AF XY:

0.00000139

AC XY:

AN XY:

717714

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:

9.07e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000827

AC:

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

May 16, 2023

The c.1291C>T (p.H431Y) alteration is located in exon 10 (coding exon 10) of the TMPRSS13 gene. This alteration results from a C to T substitution at nucleotide position 1291, causing the histidine (H) at amino acid position 431 to be replaced by a tyrosine (Y). 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

0.098

BayesDel_addAF

Pathogenic

0.20

BayesDel_noAF

Uncertain

0.040

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.32

.;T;.;T

Eigen

Uncertain

0.57

Eigen_PC

Uncertain

0.61

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.91

D;D;D;D

M_CAP

Benign

0.073

MetaRNN

Uncertain

0.46

T;T;T;T

MetaSVM

Uncertain

0.50

MutationAssessor

Benign

0.99

.;.;L;.

PrimateAI

Benign

0.41

PROVEAN

Uncertain

-2.4

N;N;N;N

REVEL

Uncertain

0.64

Sift

Uncertain

0.025

D;D;D;D

Sift4G

Uncertain

0.046

D;D;D;D

Polyphen

0.99

.;D;.;.

Vest4

0.41

MVP

0.92

MPC

0.59

ClinPred

0.95

GERP RS

5.0

gMVP

0.61

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