11-117908780-G-A

Variant names:

• chr11-117908780-G-A
• rs201380115
• NM_001077263.3:c.1114C>T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001077263.3(TMPRSS13):​c.1114C>T​(p.Arg372Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000556 in 1,601,728 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000039 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000057 (0 hom.)
• Consequence: TMPRSS13 NM_001077263.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.91

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.1906614).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TMPRSS13	NM_001077263.3	c.1114C>T	p.Arg372Trp	missense_variant	Exon 9 of 13	ENST00000524993.6	NP_001070731.1
TMPRSS13	NM_001244995.2	c.1114C>T	p.Arg372Trp	missense_variant	Exon 9 of 13		NP_001231924.1
TMPRSS13	NM_001206789.2	c.1009C>T	p.Arg337Trp	missense_variant	Exon 8 of 12		NP_001193718.1
TMPRSS13	NM_001206790.2	c.1114C>T	p.Arg372Trp	missense_variant	Exon 9 of 9		NP_001193719.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TMPRSS13	ENST00000524993.6	c.1114C>T	p.Arg372Trp	missense_variant	Exon 9 of 13	1	NM_001077263.3	ENSP00000434279.1

Frequencies

GnomAD3 genomes AF: 0.0000394 AC: 6 AN: 152180 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000131

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.0000941

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.0000569 AC: 13 AN: 228472 Hom.: 0 AF XY: 0.0000406 AC XY: 5 AN XY: 123172

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000277

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.0000528

Gnomad NFE exome AF: 0.0000193

Gnomad OTH exome AF: 0.000180

GnomAD4 exome AF: 0.0000573 AC: 83 AN: 1449430 Hom.: 0 Cov.: 31 AF XY: 0.0000500 AC XY: 36 AN XY: 719388

Gnomad4 AFR exome AF: 0.0000599

Gnomad4 AMR exome AF: 0.000231

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000120

Gnomad4 FIN exome AF: 0.000174

Gnomad4 NFE exome AF: 0.0000551

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.0000394 AC: 6 AN: 152298 Hom.: 0 Cov.: 33 AF XY: 0.0000537 AC XY: 4 AN XY: 74472

Gnomad4 AFR AF: 0.0000241

Gnomad4 AMR AF: 0.000131

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.0000941

Gnomad4 NFE AF: 0.0000294

Gnomad4 OTH AF: 0.00

Alfa AF: 0.0000784 Hom.: 0

Bravo AF: 0.0000642

ExAC AF: 0.0000580 AC: 7

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Aug 17, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1114C>T (p.R372W) alteration is located in exon 9 (coding exon 9) of the TMPRSS13 gene. This alteration results from a C to T substitution at nucleotide position 1114, causing the arginine (R) at amino acid position 372 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	0.16
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.12
CADD	Pathogenic	26
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.40	.;T;.;T;.
Eigen	Uncertain	0.46
Eigen_PC	Uncertain	0.41
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Uncertain	0.93	D;D;D;D;D
M_CAP	Uncertain	0.19	D
MetaRNN	Benign	0.19	T;T;T;T;T
MetaSVM	Uncertain	0.45	D
MutationAssessor	Benign	1.4	.;.;L;.;L
PrimateAI	Uncertain	0.48	T
PROVEAN	Benign	-1.8	N;N;N;N;N
REVEL	Benign	0.28
Sift	Benign	0.13	T;T;T;D;D
Sift4G	Uncertain	0.039	D;D;D;D;D
Polyphen		1.0	.;D;.;.;.
Vest4		0.32
MVP		0.92
MPC		0.73
ClinPred		0.23	T
GERP RS		4.1
gMVP		0.73

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: rs201380115; hg19: chr11-117779495; COSMIC: COSV105350517; COSMIC: COSV105350517;