rs774486213

Variant names:

• chr16-2785420-C-G
• rs774486213
• NM_152891.3:c.469G>C

Your query was ambiguous. Multiple possible variants found:

• chr16-2785420-C-G
• chr16-2785420-C-T

Variant summary

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

The NM_152891.3(PRSS33):​c.469G>C​(p.Gly157Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000689 in 1,451,242 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 (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G157A) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0000069 (0 hom.)
• Consequence: PRSS33 NM_152891.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.292
• Publications: 0 publications found

Genes affected

PRSS33 (HGNC:30405): (serine protease 33) Enables serine-type endopeptidase activity. Involved in protein kinase C signaling and proteolysis. Located in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

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, 0.827

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRSS33	NM_152891.3	c.469G>C	p.Gly157Arg	missense_variant	Exon 5 of 7	ENST00000682474.1	NP_690851.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRSS33	ENST00000682474.1	c.469G>C	p.Gly157Arg	missense_variant	Exon 5 of 7		NM_152891.3	ENSP00000507560.1

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152128 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000339 AC: 2 AN: 59000 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000427

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000693 AC: 9 AN: 1299114 Hom.: 0 Cov.: 33 AF XY: 0.00000471 AC XY: 3 AN XY: 637490

African (AFR) AF: 0.00 AC: 0 AN: 26236

American (AMR) AF: 0.00 AC: 0 AN: 20268

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19388

East Asian (EAS) AF: 0.0000937 AC: 3 AN: 32006

South Asian (SAS) AF: 0.0000602 AC: 4 AN: 66412

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 31424

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3806

European-Non Finnish (NFE) AF: 0.00000191 AC: 2 AN: 1045774

Other (OTH) AF: 0.00 AC: 0 AN: 53800

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152128 Hom.: 0 Cov.: 33 AF XY: 0.0000135 AC XY: 1 AN XY: 74314

African (AFR) AF: 0.00 AC: 0 AN: 41430

American (AMR) AF: 0.00 AC: 0 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5188

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10618

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 312

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67992

Other (OTH) AF: 0.00 AC: 0 AN: 2094

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ExAC AF: 0.0000110 AC: 1

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jun 29, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.469G>C (p.G157R) alteration is located in exon 4 (coding exon 4) of the PRSS33 gene. This alteration results from a G to C substitution at nucleotide position 469, causing the glycine (G) at amino acid position 157 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.33
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.17
CADD	Benign	14
DANN	Uncertain	0.98
DEOGEN2	Uncertain	0.54	D;D;D
Eigen	Benign	-0.43
Eigen_PC	Benign	-0.67
FATHMM_MKL	Benign	0.11	N
LIST_S2	Benign	0.43	.;T;T
M_CAP	Pathogenic	0.31	D
MetaRNN	Pathogenic	0.83	D;D;D
MetaSVM	Uncertain	0.080	D
MutationAssessor	Uncertain	2.2	M;M;.
PhyloP100		0.29
PrimateAI	Uncertain	0.77	T
PROVEAN	Pathogenic	-7.7	D;.;.
REVEL	Benign	0.28
Sift	Uncertain	0.0010	D;.;.
Sift4G	Uncertain	0.0030	D;D;.
Polyphen		1.0	D;D;.
Vest4		0.18
MutPred		0.75		Gain of solvent accessibility (P = 0.0097);Gain of solvent accessibility (P = 0.0097);.;
MVP		0.65
MPC		0.71
ClinPred		0.43	T
GERP RS		1.5
Varity_R		0.50
gMVP		0.68
Mutation Taster		=92/8	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: rs774486213; hg19: chr16-2835421;