11-117914457-G-A

Position:

• chr11-117914457-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The ENST00000524993.6(TMPRSS13):​c.614C>T​(p.Pro205Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/20 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)
• Consequence: TMPRSS13 ENST00000524993.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.52

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.275683).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TMPRSS13	NM_001077263.3	c.614C>T	p.Pro205Leu	missense_variant	4/13	ENST00000524993.6	NP_001070731.1
TMPRSS13	NM_001244995.2	c.614C>T	p.Pro205Leu	missense_variant	4/13		NP_001231924.1
TMPRSS13	NM_001206789.2	c.509C>T	p.Pro170Leu	missense_variant	3/12		NP_001193718.1
TMPRSS13	NM_001206790.2	c.614C>T	p.Pro205Leu	missense_variant	4/9		NP_001193719.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TMPRSS13	ENST00000524993.6	c.614C>T	p.Pro205Leu	missense_variant	4/13	1	NM_001077263.3	ENSP00000434279	A2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 05, 2022

The c.614C>T (p.P205L) alteration is located in exon 4 (coding exon 4) of the TMPRSS13 gene. This alteration results from a C to T substitution at nucleotide position 614, causing the proline (P) at amino acid position 205 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	Benign	0.13
BayesDel_addAF	Uncertain	0.059	T
BayesDel_noAF	Benign	-0.15
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.0024	.;T;.;T;.
Eigen	Benign	0.14
Eigen_PC	Uncertain	0.23
FATHMM_MKL	Benign	0.66	D
LIST_S2	Uncertain	0.94	D;D;D;D;D
M_CAP	Uncertain	0.096	D
MetaRNN	Benign	0.28	T;T;T;T;T
MetaSVM	Uncertain	-0.065	T
MutationAssessor	Benign	2.0	.;.;M;.;M
MutationTaster	Benign	1.0	D;D;D;D;D
PrimateAI	Benign	0.34	T
PROVEAN	Benign	-0.24	N;N;N;N;N
REVEL	Uncertain	0.44
Sift	Benign	0.23	T;T;T;T;T
Sift4G	Benign	0.85	T;T;T;T;D
Polyphen		0.14	.;B;.;.;.
Vest4		0.45
MutPred		0.42		.;Loss of disorder (P = 0.0139);Loss of disorder (P = 0.0139);Loss of disorder (P = 0.0139);Loss of disorder (P = 0.0139);
MVP		0.95
MPC		0.27
ClinPred		0.69	D
GERP RS		3.9
gMVP		0.46

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

Other links and lift over

dbSNP: rs2057555031; hg19: chr11-117785172;