rs750270352

Variant names:

• chr19-685787-C-G
• rs750270352
• NM_001308209.2:c.778G>C

Your query was ambiguous. Multiple possible variants found:

• chr19-685787-C-G
• chr19-685787-C-T

Variant summary

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

The NM_001308209.2(PRSS57):​c.778G>C​(p.Val260Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000141 in 1,414,386 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V260M) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: PRSS57 NM_001308209.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.322
• Publications: 0 publications found

Genes affected

PRSS57 (HGNC:31397): (serine protease 57) This gene encodes an arginine-specific serine protease and member of the peptidase S1 family of proteins. The encoded protein may undergo proteolytic activation before storage in azurophil granules, in neutrophil cells of the immune system. Following neutrophil activation, the protease is released into the pericellular environment, where it may play a role in defense against microbial pathogens. [provided by RefSeq, Jul 2016]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001308209.2. 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
	PRSS57	NM_001308209.2	MANE Select	c.778G>C	p.Val260Leu	missense	Exon 5 of 5	NP_001295138.2	A0A0A0MR61
	PRSS57	NM_214710.5		c.781G>C	p.Val261Leu	missense	Exon 5 of 5	NP_999875.2	Q6UWY2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRSS57	ENST00000329267.9	TSL:1 MANE Select	c.778G>C	p.Val260Leu	missense	Exon 5 of 5	ENSP00000327386.6	A0A0A0MR61
	PRSS57	ENST00000613411.4	TSL:1	c.781G>C	p.Val261Leu	missense	Exon 5 of 5	ENSP00000482358.1	Q6UWY2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000556 AC: 1 AN: 179990 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000362

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000141 AC: 2 AN: 1414386 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 698590

African (AFR) AF: 0.00 AC: 0 AN: 32380

American (AMR) AF: 0.0000514 AC: 2 AN: 38914

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25304

East Asian (EAS) AF: 0.00 AC: 0 AN: 36940

South Asian (SAS) AF: 0.00 AC: 0 AN: 80568

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49542

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5666

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1086662

Other (OTH) AF: 0.00 AC: 0 AN: 58410

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

ClinVar

ClinVar submissions as Germline

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	0.33
BayesDel_addAF	Benign	-0.10	T
BayesDel_noAF	Benign	-0.27
CADD	Benign	19
DANN	Uncertain	0.99
DEOGEN2	Benign	0.048	T
Eigen	Benign	-0.065
Eigen_PC	Benign	-0.24
FATHMM_MKL	Benign	0.49	N
LIST_S2	Benign	0.51	T
M_CAP	Pathogenic	0.41	D
MetaRNN	Uncertain	0.52	D
MetaSVM	Uncertain	0.71	D
MutationAssessor	Benign	1.8	L
PhyloP100		0.32
PrimateAI	Uncertain	0.49	T
REVEL	Uncertain	0.56
Sift4G	Uncertain	0.018	D
Polyphen		0.99	D
Vest4		0.42
MutPred		0.52		Loss of MoRF binding (P = 0.1026)
MVP		0.54
MPC		0.050
ClinPred		0.86	D
GERP RS		3.7
Varity_R		0.82
gMVP		0.68
Mutation Taster		=65/35	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: rs750270352; hg19: chr19-685787;