11-117905648-C-A

Variant names:

• chr11-117905648-C-A
• rs201556502
• NM_001077263.3:c.1371G>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001077263.3(TMPRSS13):​c.1371G>T​(p.Arg457Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000329 in 1,600,486 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00020 (0 hom., cov: 31)
  • Exomes 𝑓: 0.00034 (1 hom.)
• Consequence: TMPRSS13 NM_001077263.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.193
• Publications: 2 publications found

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

Our verdict: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.07021284).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001077263.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMPRSS13	NM_001077263.3	MANE Select	c.1371G>T	p.Arg457Ser	missense	Exon 10 of 13	NP_001070731.1	Q9BYE2-6
	TMPRSS13	NM_001244995.2		c.1371G>T	p.Arg457Ser	missense	Exon 10 of 13	NP_001231924.1	Q9BYE2-2
	TMPRSS13	NM_001206789.2		c.1266G>T	p.Arg422Ser	missense	Exon 9 of 12	NP_001193718.1	Q9BYE2-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMPRSS13	ENST00000524993.6	TSL:1 MANE Select	c.1371G>T	p.Arg457Ser	missense	Exon 10 of 13	ENSP00000434279.1	Q9BYE2-6
	TMPRSS13	ENST00000445164.6	TSL:1	c.1371G>T	p.Arg457Ser	missense	Exon 10 of 12	ENSP00000394114.2	Q9BYE2-1
	TMPRSS13	ENST00000430170.6	TSL:1	c.1371G>T	p.Arg457Ser	missense	Exon 10 of 13	ENSP00000387702.2	Q9BYE2-2

Frequencies

GnomAD3 genomes AF: 0.000197 AC: 30 AN: 152188 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.0000724

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000196

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: 0.000353

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000103 AC: 24 AN: 232058 AF XY: 0.000112

Gnomad AFR exome AF: 0.0000699

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0000504

Gnomad NFE exome AF: 0.000183

Gnomad OTH exome AF: 0.000520

GnomAD4 exome AF: 0.000343 AC: 497 AN: 1448298 Hom.: 1 Cov.: 30 AF XY: 0.000369 AC XY: 265 AN XY: 719002

African (AFR) AF: 0.0000600 AC: 2 AN: 33322

American (AMR) AF: 0.0000459 AC: 2 AN: 43582

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25764

East Asian (EAS) AF: 0.00 AC: 0 AN: 39506

South Asian (SAS) AF: 0.00 AC: 0 AN: 83858

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52742

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5740

European-Non Finnish (NFE) AF: 0.000433 AC: 478 AN: 1103962

Other (OTH) AF: 0.000251 AC: 15 AN: 59822

GnomAD4 genome AF: 0.000197 AC: 30 AN: 152188 Hom.: 0 Cov.: 31 AF XY: 0.000148 AC XY: 11 AN XY: 74356

African (AFR) AF: 0.0000724 AC: 3 AN: 41448

American (AMR) AF: 0.000196 AC: 3 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5190

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.000353 AC: 24 AN: 68026

Other (OTH) AF: 0.00 AC: 0 AN: 2094

Alfa AF: 0.000277 Hom.: 0

Bravo AF: 0.000166

TwinsUK AF: 0.000539 AC: 2

ALSPAC AF: 0.000519 AC: 2

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000355 AC: 3

ExAC AF: 0.000124 AC: 15

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.27
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.30
CADD	Benign	14
DANN	Uncertain	0.98
DEOGEN2	Benign	0.18	T
Eigen	Benign	-0.58
Eigen_PC	Benign	-0.48
FATHMM_MKL	Benign	0.70	D
LIST_S2	Benign	0.75	T
M_CAP	Benign	0.066	D
MetaRNN	Benign	0.070	T
MetaSVM	Benign	-0.62	T
MutationAssessor	Benign	-0.46	N
PhyloP100		-0.19
PrimateAI	Benign	0.34	T
PROVEAN	Benign	-1.3	N
REVEL	Benign	0.23
Sift	Benign	0.37	T
Sift4G	Benign	0.35	T
Polyphen		0.62	P
Vest4		0.11
MVP		0.78
MPC		0.26
ClinPred		0.030	T
GERP RS		2.0
gMVP		0.56
Mutation Taster		=89/11	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs201556502; hg19: chr11-117776363;