chr16-2785378-C-G

Variant names:

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

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_152891.3(PRSS33):​c.511G>C​(p.Gly171Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000779 in 1,283,418 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 7.8e-7 (0 hom.)
• Consequence: PRSS33 NM_152891.3 missense
• Clinical Significance: Not reported in ClinVar
• 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: Uncertain_significance. The variant received 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
PRSS33	NM_152891.3	c.511G>C	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>C	p.Gly171Arg	missense_variant	Exon 5 of 7		NM_152891.3	ENSP00000507560.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 7.79e-7 AC: 1 AN: 1283418 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 624982

African (AFR) AF: 0.00 AC: 0 AN: 26778

American (AMR) AF: 0.0000541 AC: 1 AN: 18468

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18348

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

South Asian (SAS) AF: 0.00 AC: 0 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: 0.00 AC: 0 AN: 1036972

Other (OTH) AF: 0.00 AC: 0 AN: 53166

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.33
BayesDel_addAF	Uncertain	0.14	D
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	Pathogenic	0.97	D
LIST_S2	Benign	0.60	.;T;T
M_CAP	Pathogenic	0.62	D
MetaRNN	Uncertain	0.69	D;D;D
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		0.98	D
GERP RS		4.6
Varity_R		0.12
gMVP		0.72

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;