chr19-685864-G-A

Variant names:

• chr19-685864-G-A
• rs372449854
• NM_001308209.2:c.701C>T

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_001308209.2(PRSS57):​c.701C>T​(p.Ser234Leu) variant causes a missense change. The variant allele was found at a frequency of 0.0000494 in 1,557,808 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000033 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000051 (0 hom.)
• Consequence: PRSS57 NM_001308209.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.03
• 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 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.82

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.701C>T	p.Ser234Leu	missense	Exon 5 of 5	NP_001295138.2	A0A0A0MR61
	PRSS57	NM_214710.5		c.704C>T	p.Ser235Leu	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.701C>T	p.Ser234Leu	missense	Exon 5 of 5	ENSP00000327386.6	A0A0A0MR61
	PRSS57	ENST00000613411.4	TSL:1	c.704C>T	p.Ser235Leu	missense	Exon 5 of 5	ENSP00000482358.1	Q6UWY2

Frequencies

GnomAD3 genomes AF: 0.0000329 AC: 5 AN: 151980 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000725

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

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: 0.0000294

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000428 AC: 7 AN: 163690 AF XY: 0.0000343

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.000233

Gnomad EAS exome AF: 0.0000829

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000153

Gnomad OTH exome AF: 0.000439

GnomAD4 exome AF: 0.0000512 AC: 72 AN: 1405828 Hom.: 0 Cov.: 31 AF XY: 0.0000547 AC XY: 38 AN XY: 694262

African (AFR) AF: 0.0000312 AC: 1 AN: 32046

American (AMR) AF: 0.00 AC: 0 AN: 36848

Ashkenazi Jewish (ASJ) AF: 0.000159 AC: 4 AN: 25236

East Asian (EAS) AF: 0.0000275 AC: 1 AN: 36422

South Asian (SAS) AF: 0.000100 AC: 8 AN: 79800

European-Finnish (FIN) AF: 0.0000416 AC: 2 AN: 48070

Middle Eastern (MID) AF: 0.000175 AC: 1 AN: 5702

European-Non Finnish (NFE) AF: 0.0000443 AC: 48 AN: 1083414

Other (OTH) AF: 0.000120 AC: 7 AN: 58290

GnomAD4 genome AF: 0.0000329 AC: 5 AN: 151980 Hom.: 0 Cov.: 32 AF XY: 0.0000404 AC XY: 3 AN XY: 74220

African (AFR) AF: 0.0000725 AC: 3 AN: 41386

American (AMR) AF: 0.00 AC: 0 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5166

South Asian (SAS) AF: 0.00 AC: 0 AN: 4802

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10610

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

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 67970

Other (OTH) AF: 0.00 AC: 0 AN: 2090

Alfa AF: 0.0000434 Hom.: 0

Bravo AF: 0.0000227

TwinsUK AF: 0.00 AC: 0

ALSPAC AF: 0.000259 AC: 1

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000118 AC: 1

ExAC AF: 0.0000175 AC: 2

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	Pathogenic	0.71
BayesDel_addAF	Uncertain	0.15	D
BayesDel_noAF	Uncertain	-0.020
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.53	D
Eigen	Uncertain	0.35
Eigen_PC	Uncertain	0.30
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Benign	0.82	T
M_CAP	Pathogenic	0.32	D
MetaRNN	Pathogenic	0.82	D
MetaSVM	Uncertain	0.73	D
MutationAssessor	Benign	2.0	M
PhyloP100		4.0
PrimateAI	Uncertain	0.68	T
REVEL	Pathogenic	0.79
Sift4G	Uncertain	0.0050	D
Polyphen		1.0	D
Vest4		0.65
MVP		0.43
MPC		0.11
ClinPred		0.47	T
GERP RS		4.8
Varity_R		0.62
gMVP		0.72
Mutation Taster		=61/39	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: rs372449854; hg19: chr19-685864;