NM_152891.3:c.470G>A

Variant names:

• chr16-2785419-C-T
• rs2068861509
• NM_152891.3:c.470G>A

Variant summary

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

The NM_152891.3(PRSS33):​c.470G>A​(p.Gly157Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000231 in 1,299,726 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic 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. G157A) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000023 (0 hom.)
• Consequence: PRSS33 NM_152891.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.409
• 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, 0.824

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRSS33	NM_152891.3	c.470G>A	p.Gly157Asp	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.470G>A	p.Gly157Asp	missense_variant	Exon 5 of 7		NM_152891.3	ENSP00000507560.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000231 AC: 3 AN: 1299726 Hom.: 0 Cov.: 33 AF XY: 0.00000314 AC XY: 2 AN XY: 637652

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 26342

American (AMR) AF: 0.00 AC: 0 AN: 20392

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19364

East Asian (EAS) AF: 0.00 AC: 0 AN: 32156

South Asian (SAS) AF: 0.0000151 AC: 1 AN: 66402

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 31434

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3824

European-Non Finnish (NFE) AF: 0.00000191 AC: 2 AN: 1045980

Other (OTH) AF: 0.00 AC: 0 AN: 53832

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.23
BayesDel_addAF	Uncertain	0.052	T
BayesDel_noAF	Benign	-0.16
CADD	Benign	20
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.50	D;D;D
Eigen	Benign	0.071
Eigen_PC	Benign	-0.13
FATHMM_MKL	Benign	0.11	N
LIST_S2	Benign	0.39	.;T;T
M_CAP	Pathogenic	0.48	D
MetaRNN	Pathogenic	0.82	D;D;D
MetaSVM	Uncertain	0.34	D
MutationAssessor	Benign	1.9	L;L;.
PhyloP100		0.41
PrimateAI	Uncertain	0.78	T
PROVEAN	Pathogenic	-6.8	D;.;.
REVEL	Uncertain	0.43
Sift	Benign	0.039	D;.;.
Sift4G	Uncertain	0.055	T;T;.
Polyphen		1.0	D;D;.
Vest4		0.34
MutPred		0.70		Gain of solvent accessibility (P = 0.1014);Gain of solvent accessibility (P = 0.1014);.;
MVP		0.82
MPC		1.2
ClinPred		0.93	D
GERP RS		4.7
Varity_R		0.45
gMVP		0.64

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: rs2068861509; hg19: chr16-2835420;