NM_152891.3:c.511G>A

Variant names:

• chr16-2785378-C-T
• rs768346321
• NM_152891.3:c.511G>A

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BP4

The NM_152891.3(PRSS33):​c.511G>A​(p.Gly171Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000223 in 1,435,628 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00014 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00023 (0 hom.)
• Consequence: PRSS33 NM_152891.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.67
• 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: Likely_benign. The variant received -1 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.3251556).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRSS33	NM_152891.3	c.511G>A	p.Gly171Arg	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.511G>A	p.Gly171Arg	missense_variant	Exon 5 of 7		NM_152891.3	ENSP00000507560.1

Frequencies

GnomAD3 genomes AF: 0.000145 AC: 22 AN: 152210 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000965

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000131

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000221

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000177 AC: 9 AN: 50990 AF XY: 0.000186

Gnomad AFR exome AF: 0.000268

Gnomad AMR exome AF: 0.000115

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000208

Gnomad OTH exome AF: 0.000627

GnomAD4 exome AF: 0.000232 AC: 298 AN: 1283418 Hom.: 0 Cov.: 33 AF XY: 0.000218 AC XY: 136 AN XY: 624982

African (AFR) AF: 0.0000373 AC: 1 AN: 26778

American (AMR) AF: 0.000108 AC: 2 AN: 18468

Ashkenazi Jewish (ASJ) AF: 0.000164 AC: 3 AN: 18348

East Asian (EAS) AF: 0.00 AC: 0 AN: 32944

South Asian (SAS) AF: 0.0000961 AC: 6 AN: 62408

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 30476

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3858

European-Non Finnish (NFE) AF: 0.000267 AC: 277 AN: 1036972

Other (OTH) AF: 0.000169 AC: 9 AN: 53166

GnomAD4 genome AF: 0.000145 AC: 22 AN: 152210 Hom.: 0 Cov.: 33 AF XY: 0.000148 AC XY: 11 AN XY: 74360

African (AFR) AF: 0.0000965 AC: 4 AN: 41456

American (AMR) AF: 0.000131 AC: 2 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.000288 AC: 1 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5196

South Asian (SAS) AF: 0.00 AC: 0 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10626

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

European-Non Finnish (NFE) AF: 0.000221 AC: 15 AN: 68018

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

Alfa AF: 0.000139 Hom.: 0

Bravo AF: 0.000132

ExAC AF: 0.0000840 AC: 8

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Apr 19, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.511G>A (p.G171R) alteration is located in exon 4 (coding exon 4) of the PRSS33 gene. This alteration results from a G to A substitution at nucleotide position 511, causing the glycine (G) at amino acid position 171 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	-0.069	T
BayesDel_noAF	Uncertain	-0.040
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.44	T;T;D
Eigen	Uncertain	0.30
Eigen_PC	Uncertain	0.29
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Benign	0.60	.;T;T
M_CAP	Pathogenic	0.62	D
MetaRNN	Benign	0.33	T;T;T
MetaSVM	Uncertain	0.46	D
MutationAssessor	Benign	1.6	L;L;.
PhyloP100		2.7
PrimateAI	Pathogenic	0.79	T
PROVEAN	Benign	-1.6	N;.;.
REVEL	Uncertain	0.64
Sift	Benign	0.091	T;.;.
Sift4G	Uncertain	0.050	T;T;.
Polyphen		0.85	P;P;.
Vest4		0.33
MutPred		0.44		Gain of solvent accessibility (P = 0.0037);Gain of solvent accessibility (P = 0.0037);.;
MVP		0.78
MPC		1.2
ClinPred		0.13	T
GERP RS		4.6
Varity_R		0.12
gMVP		0.72
Mutation Taster		=64/36	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: rs768346321; hg19: chr16-2835379;