rs193920873

Positions:

• chr16-2853241-C-G
• chr16-2853241-C-T

Variant summary

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

The NM_022119.4(PRSS22):​c.806G>C​(p.Arg269Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000187 in 1,600,736 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R269H) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000013 (0 hom., cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: PRSS22 NM_022119.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.321

Genes affected

PRSS22 (HGNC:14368): (serine protease 22) This gene encodes a member of the trypsin family of serine proteases. The enzyme is expressed in the airways in a developmentally regulated manner. The gene is part of a cluster of serine protease genes on chromosome 16. [provided by RefSeq, Jul 2008]

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=0.08786583).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PRSS22	NM_022119.4	c.806G>C	p.Arg269Pro	missense_variant	6/6	ENST00000161006.8
PRSS22	XM_047434451.1	c.593G>C	p.Arg198Pro	missense_variant	4/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PRSS22	ENST00000161006.8	c.806G>C	p.Arg269Pro	missense_variant	6/6	1	NM_022119.4	P1
PRSS22	ENST00000576381.2	c.*664G>C		3_prime_UTR_variant, NMD_transcript_variant	6/6	1
PRSS22	ENST00000571228.1	c.476G>C	p.Arg159Pro	missense_variant	5/5	2
PRSS22	ENST00000575164.1	n.658G>C		non_coding_transcript_exon_variant	3/3	2

Frequencies

GnomAD3 genomes AF: 0.0000131 AC: 2 AN: 152114 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000241

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: 0.0000147

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 6.90e-7 AC: 1 AN: 1448622 Hom.: 0 Cov.: 33 AF XY: 0.00000139 AC XY: 1 AN XY: 721200

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: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.0000131 AC: 2 AN: 152114 Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1 AN XY: 74306

Gnomad4 AFR AF: 0.0000241

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000147

Gnomad4 OTH AF: 0.00

Bravo AF: 0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.19
BayesDel_addAF	Uncertain	0.051	T
BayesDel_noAF	Benign	-0.16
CADD	Benign	22
DANN	Benign	0.86
DEOGEN2	Benign	0.16	T;.
Eigen	Benign	-0.85
Eigen_PC	Benign	-0.69
FATHMM_MKL	Benign	0.057	N
M_CAP	Benign	0.079	D
MetaRNN	Benign	0.088	T;T
MetaSVM	Benign	-0.74	T
MutationAssessor	Benign	-1.4	N;.
MutationTaster	Benign	0.93	N;N
PrimateAI	Uncertain	0.69	T
PROVEAN	Benign	-1.0	N;.
REVEL	Uncertain	0.48
Sift	Benign	0.31	T;.
Sift4G	Benign	0.23	T;T
Polyphen		0.026	B;.
Vest4		0.23
MutPred		0.50		Gain of glycosylation at R269 (P = 0.0506);.;
MVP		0.58
MPC		0.48
ClinPred		0.38	T
GERP RS		3.1
Varity_R		0.31
gMVP		0.91

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

Publications

LitVar

Other links and lift over

dbSNP: rs193920873; hg19: chr16-2903242;