19-694958-C-T

Variant names:

• chr19-694958-C-T
• rs776563968
• NM_001308209.2:c.89G>A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001308209.2(PRSS57):​c.89G>A​(p.Gly30Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000151 in 1,392,742 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.000015 (1 hom.)
• Consequence: PRSS57 NM_001308209.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0770

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.16058454).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRSS57	NM_001308209.2	c.89G>A	p.Gly30Glu	missense_variant	Exon 2 of 5	ENST00000329267.9	NP_001295138.2
PRSS57	NM_214710.5	c.92G>A	p.Gly31Glu	missense_variant	Exon 2 of 5		NP_999875.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRSS57	ENST00000329267.9	c.89G>A	p.Gly30Glu	missense_variant	Exon 2 of 5	1	NM_001308209.2	ENSP00000327386.6
PRSS57	ENST00000613411.4	c.92G>A	p.Gly31Glu	missense_variant	Exon 2 of 5	1		ENSP00000482358.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD3 exomes AF: 0.00000584 AC: 1 AN: 171216 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 93960

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 SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000130

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000151 AC: 21 AN: 1392742 Hom.: 1 Cov.: 31 AF XY: 0.0000116 AC XY: 8 AN XY: 688398

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000300

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: 0.0000176

Gnomad4 OTH exome AF: 0.0000175

GnomAD4 genome Cov.: 31

Bravo AF: 0.0000113

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.46
CADD	Benign	18
DANN	Benign	0.95
DEOGEN2	Benign	0.048	T;T
Eigen	Benign	-0.98
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.094	N
LIST_S2	Benign	0.48	T;T
M_CAP	Uncertain	0.15	D
MetaRNN	Benign	0.16	T;T
MetaSVM	Benign	-0.38	T
MutationAssessor	Benign	0.0	N;.
PrimateAI	Benign	0.42	T
REVEL	Benign	0.23
Sift4G	Uncertain	0.012	D;D
Polyphen		0.60	P;.
Vest4		0.42
MutPred		0.43		Gain of catalytic residue at G31 (P = 0.0531);.;
MVP		0.12
MPC		0.059
ClinPred		0.29	T
GERP RS		-4.4
Varity_R		0.13
gMVP		0.40

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.090		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs776563968; hg19: chr19-694958;