chr19-691859-C-A

Variant names:

• chr19-691859-C-A
• NM_001308209.2:c.377G>T

Variant summary

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

The NM_001308209.2(PRSS57):​c.377G>T​(p.Arg126Leu) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000849 in 1,177,576 control chromosomes in the GnomAD database, with no homozygous occurrence. 12/21 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 8.5e-7 (0 hom.)
• Consequence: PRSS57 NM_001308209.2 missense, splice_region
• Scores: Splicing: ADA: 0.0008788
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.572

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

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
PRSS57	NM_001308209.2	c.377G>T	p.Arg126Leu	missense_variant, splice_region_variant	Exon 3 of 5	ENST00000329267.9	NP_001295138.2
PRSS57	NM_214710.5	c.380G>T	p.Arg127Leu	missense_variant, splice_region_variant	Exon 3 of 5		NP_999875.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRSS57	ENST00000329267.9	c.377G>T	p.Arg126Leu	missense_variant, splice_region_variant	Exon 3 of 5	1	NM_001308209.2	ENSP00000327386.6
PRSS57	ENST00000613411.4	c.380G>T	p.Arg127Leu	missense_variant, splice_region_variant	Exon 3 of 5	1		ENSP00000482358.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 8.49e-7 AC: 1 AN: 1177576 Hom.: 0 Cov.: 29 AF XY: 0.00 AC XY: 0 AN XY: 566340

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000104

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.21
BayesDel_addAF	Benign	-0.10	T
BayesDel_noAF	Benign	-0.38
CADD	Benign	12
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.52	D;T
Eigen	Benign	-0.50
Eigen_PC	Benign	-0.58
FATHMM_MKL	Benign	0.12	N
LIST_S2	Benign	0.56	T;T
M_CAP	Uncertain	0.28	D
MetaRNN	Uncertain	0.53	D;D
MetaSVM	Uncertain	-0.25	T
MutationAssessor	Benign	1.4	L;.
PrimateAI	Benign	0.29	T
REVEL	Uncertain	0.52
Sift4G	Uncertain	0.010	D;D
Polyphen		0.64	P;.
Vest4		0.24
MutPred		0.69		Loss of sheet (P = 0.1501);.;
MVP		0.24
MPC		0.016
ClinPred		0.86	D
GERP RS		-0.28
Varity_R		0.56
gMVP		0.50

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00088
dbscSNV1_RF	Benign	0.070
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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr19-691859; COSMIC: COSV100249567; COSMIC: COSV100249567;