Variant 11-117910731-G-A 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.922C>T(p.Arg308Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000746 in 1,608,620 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00016 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000066 ( 0 hom. )

Consequence

TMPRSS13
NM_001077263.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.671

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=0.10246265).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TMPRSS13	NM_001077263.3 linkuse as main transcript	c.922C>T	p.Arg308Trp	missense_variant	7/13	ENST00000524993.6	NP_001070731.1	Q9BYE2-6
TMPRSS13	NM_001244995.2 linkuse as main transcript	c.922C>T	p.Arg308Trp	missense_variant	7/13		NP_001231924.1	Q9BYE2-2
TMPRSS13	NM_001206789.2 linkuse as main transcript	c.817C>T	p.Arg273Trp	missense_variant	6/12		NP_001193718.1	Q9BYE2-3
TMPRSS13	NM_001206790.2 linkuse as main transcript	c.922C>T	p.Arg308Trp	missense_variant	7/9		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.922C>T	p.Arg308Trp	missense_variant	7/13	1	NM_001077263.3	ENSP00000434279.1		Q9BYE2-6

Frequencies

GnomAD3 genomes

AF:

0.000158

AC:

AN:

152066

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000242

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

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:

0.000323

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000998

AC:

AN:

240406

Hom.:

AF XY:

0.0000846

AC XY:

AN XY:

130054

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.000101

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000480

Gnomad NFE exome

AF:

0.000194

Gnomad OTH exome

AF:

0.000169

GnomAD4 exome

AF:

0.0000659

AC:

AN:

1456436

Hom.:

Cov.:

AF XY:

0.0000511

AC XY:

AN XY:

723830

show subpopulations

Gnomad4 AFR exome

AF:

0.0000300

Gnomad4 AMR exome

AF:

0.0000226

Gnomad4 ASJ exome

AF:

0.0000384

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000377

Gnomad4 NFE exome

AF:

0.0000785

Gnomad4 OTH exome

AF:

0.0000664

GnomAD4 genome

AF:

0.000158

AC:

AN:

152184

Hom.:

Cov.:

AF XY:

0.000148

AC XY:

AN XY:

74394

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000323

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.00793

Hom.:

813

Bravo

AF:

0.000117

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000121

AC:

ExAC

AF:

0.000132

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 08, 2023

The c.922C>T (p.R308W) alteration is located in exon 7 (coding exon 7) of the TMPRSS13 gene. This alteration results from a C to T substitution at nucleotide position 922, causing the arginine (R) at amino acid position 308 to be replaced by a tryptophan (W). 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

0.13

BayesDel_addAF

Benign

-0.36

BayesDel_noAF

Benign

-0.42

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.11

.;T;.;T;.

Eigen

Benign

-0.0061

Eigen_PC

Benign

-0.12

FATHMM_MKL

Benign

0.63

LIST_S2

Uncertain

0.93

D;D;D;D;D

M_CAP

Benign

0.054

MetaRNN

Benign

0.10

T;T;T;T;T

MetaSVM

Benign

-0.96

MutationAssessor

Benign

1.9

.;.;M;.;M

PrimateAI

Benign

0.25

PROVEAN

Uncertain

-3.3

D;D;D;D;D

REVEL

Benign

0.097

Sift

Uncertain

0.0090

D;D;D;D;D

Sift4G

Uncertain

0.0090

D;D;D;D;D

Polyphen

1.0

.;D;.;.;.

Vest4

0.26

MVP

0.75

MPC

0.73

ClinPred

0.51

GERP RS

3.1

gMVP

0.60

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.090

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