11-117904080-C-T

Variant names:

• chr11-117904080-C-T
• rs200481694
• NM_001077263.3:c.1403G>A

Variant summary

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

The NM_001077263.3(TMPRSS13):​c.1403G>A​(p.Arg468Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000695 in 1,614,042 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).

• Frequency:
  • Genomes: 𝑓 0.00051 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00071 (1 hom.)
• Consequence: TMPRSS13 NM_001077263.3 missense
• Clinical Significance: Uncertain significance criteria provided, multiple submitters, no conflicts U:2
• Conservation: PhyloP100: 1.41

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TMPRSS13	NM_001077263.3	c.1403G>A	p.Arg468Gln	missense_variant	Exon 11 of 13	ENST00000524993.6	NP_001070731.1
TMPRSS13	NM_001244995.2	c.1403G>A	p.Arg468Gln	missense_variant	Exon 11 of 13		NP_001231924.1
TMPRSS13	NM_001206789.2	c.1298G>A	p.Arg433Gln	missense_variant	Exon 10 of 12		NP_001193718.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TMPRSS13	ENST00000524993.6	c.1403G>A	p.Arg468Gln	missense_variant	Exon 11 of 13	1	NM_001077263.3	ENSP00000434279.1
TMPRSS13	ENST00000445164.6	c.1403G>A	p.Arg468Gln	missense_variant	Exon 11 of 12	1		ENSP00000394114.2
TMPRSS13	ENST00000430170.6	c.1403G>A	p.Arg468Gln	missense_variant	Exon 11 of 13	1		ENSP00000387702.2
TMPRSS13	ENST00000528626.5	c.1298G>A	p.Arg433Gln	missense_variant	Exon 10 of 12	1		ENSP00000435813.1

Frequencies

GnomAD3 genomes AF: 0.000506 AC: 77 AN: 152194 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000265

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000654

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00160

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000691

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.000698 AC: 174 AN: 249126 Hom.: 0 AF XY: 0.000651 AC XY: 88 AN XY: 135142

Gnomad AFR exome AF: 0.000258

Gnomad AMR exome AF: 0.0000871

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000426

Gnomad FIN exome AF: 0.00279

Gnomad NFE exome AF: 0.000813

Gnomad OTH exome AF: 0.000331

GnomAD4 exome AF: 0.000714 AC: 1044 AN: 1461730 Hom.: 1 Cov.: 36 AF XY: 0.000692 AC XY: 503 AN XY: 727164

Gnomad4 AFR exome AF: 0.0000597

Gnomad4 AMR exome AF: 0.0000671

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000325

Gnomad4 FIN exome AF: 0.00219

Gnomad4 NFE exome AF: 0.000785

Gnomad4 OTH exome AF: 0.000348

GnomAD4 genome AF: 0.000506 AC: 77 AN: 152312 Hom.: 0 Cov.: 32 AF XY: 0.000510 AC XY: 38 AN XY: 74482

Gnomad4 AFR AF: 0.000265

Gnomad4 AMR AF: 0.0000653

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00160

Gnomad4 NFE AF: 0.000691

Gnomad4 OTH AF: 0.00

Alfa AF: 0.000417 Hom.: 0

Bravo AF: 0.000348

TwinsUK AF: 0.000809 AC: 3

ALSPAC AF: 0.000259 AC: 1

ESP6500AA AF: 0.000739 AC: 3

ESP6500EA AF: 0.000240 AC: 2

ExAC AF: 0.000678 AC: 82

Asia WGS AF: 0.000289 AC: 1 AN: 3478

EpiCase AF: 0.000763

EpiControl AF: 0.000830

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Uncertain:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jun 28, 2020

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_addAF	Benign	-0.33	T
BayesDel_noAF	Benign	-0.33
CADD	Pathogenic	35
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.18	.;T;.;T
Eigen	Benign	0.062
Eigen_PC	Benign	0.20
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Uncertain	0.89	D;D;D;D
M_CAP	Benign	0.027	D
MetaRNN	Benign	0.017	T;T;T;T
MetaSVM	Benign	-0.72	T
MutationAssessor	Benign	-0.17	.;.;N;.
PrimateAI	Benign	0.39	T
PROVEAN	Benign	-1.0	N;N;N;N
REVEL	Benign	0.19
Sift	Benign	0.32	T;T;T;T
Sift4G	Benign	0.25	T;T;T;T
Polyphen		1.0	.;D;.;.
Vest4		0.23
MVP		0.70
MPC		0.29
ClinPred		0.024	T
GERP RS		5.0
gMVP		0.75

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.86		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.86		Position offset: -2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs200481694; hg19: chr11-117774795;