NM_001077263.3:c.1502G>A

Variant names:

• chr11-117903981-C-T
• rs774027435
• NM_001077263.3:c.1502G>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001077263.3(TMPRSS13):​c.1502G>A​(p.Arg501His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000013 in 1,612,408 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.000033 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000011 (0 hom.)
• Consequence: TMPRSS13 NM_001077263.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.476
• Publications: 0 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.14954823).

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.1502G>A	p.Arg501His	missense	Exon 11 of 13	NP_001070731.1	Q9BYE2-6
	TMPRSS13	NM_001244995.2		c.1502G>A	p.Arg501His	missense	Exon 11 of 13	NP_001231924.1	Q9BYE2-2
	TMPRSS13	NM_001206789.2		c.1397G>A	p.Arg466His	missense	Exon 10 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.1502G>A	p.Arg501His	missense	Exon 11 of 13	ENSP00000434279.1	Q9BYE2-6
	TMPRSS13	ENST00000445164.6	TSL:1	c.1502G>A	p.Arg501His	missense	Exon 11 of 12	ENSP00000394114.2	Q9BYE2-1
	TMPRSS13	ENST00000430170.6	TSL:1	c.1502G>A	p.Arg501His	missense	Exon 11 of 13	ENSP00000387702.2	Q9BYE2-2

Frequencies

GnomAD3 genomes AF: 0.0000329 AC: 5 AN: 152144 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000483

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000163 AC: 4 AN: 245522 AF XY: 0.0000300

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000898

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000110 AC: 16 AN: 1460264 Hom.: 0 Cov.: 36 AF XY: 0.0000151 AC XY: 11 AN XY: 726274

African (AFR) AF: 0.00 AC: 0 AN: 33428

American (AMR) AF: 0.00 AC: 0 AN: 44534

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26078

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39660

South Asian (SAS) AF: 0.0000933 AC: 8 AN: 85756

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53342

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00000450 AC: 5 AN: 1111336

Other (OTH) AF: 0.0000331 AC: 2 AN: 60362

GnomAD4 genome AF: 0.0000329 AC: 5 AN: 152144 Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1 AN XY: 74324

African (AFR) AF: 0.0000483 AC: 2 AN: 41416

American (AMR) AF: 0.00 AC: 0 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5188

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

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10618

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

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 68010

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000151

ExAC AF: 0.0000331 AC: 4

Asia WGS AF: 0.000866 AC: 3 AN: 3478

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	0.081
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.39
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.30	T
Eigen	Benign	-0.27
Eigen_PC	Benign	-0.40
FATHMM_MKL	Benign	0.026	N
LIST_S2	Benign	0.76	T
M_CAP	Benign	0.025	D
MetaRNN	Benign	0.15	T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	1.3	L
PhyloP100		0.48
PrimateAI	Benign	0.35	T
PROVEAN	Benign	-2.1	N
REVEL	Benign	0.15
Sift	Uncertain	0.010	D
Sift4G	Uncertain	0.031	D
Polyphen		0.99	D
Vest4		0.16
MVP		0.75
MPC		0.31
ClinPred		0.61	D
GERP RS		0.85
gMVP		0.45
Mutation Taster		=84/16	polymorphism

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

Other links and lift over

dbSNP: rs774027435; hg19: chr11-117774696;