16-31084843-G-C

Position:

• chr16-31084843-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001039503.3(PRSS53):​c.1216C>G​(p.Pro406Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.404 in 1,550,410 control chromosomes in the GnomAD database, including 134,886 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.45 (16795 hom., cov: 34)
  • Exomes 𝑓: 0.40 (118091 hom.)
• Consequence: PRSS53 NM_001039503.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.410

Genes affected

PRSS53 (HGNC:34407): (serine protease 53) Predicted to enable serine-type endopeptidase activity. Predicted to be involved in proteolysis. Predicted to be located in extracellular region. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=2.0032016E-6).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.694 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PRSS53	NM_001039503.3	c.1216C>G	p.Pro406Ala	missense_variant	8/11	ENST00000280606.7	NP_001034592.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PRSS53	ENST00000280606.7	c.1216C>G	p.Pro406Ala	missense_variant	8/11	1	NM_001039503.3	ENSP00000280606	P1
PRSS53	ENST00000486499.1	n.4083C>G		non_coding_transcript_exon_variant	2/2	2

Frequencies

GnomAD3 genomes AF: 0.452 AC: 68682 AN: 152022 Hom.: 16757 Cov.: 34

Gnomad AFR AF: 0.617

Gnomad AMI AF: 0.370

Gnomad AMR AF: 0.423

Gnomad ASJ AF: 0.301

Gnomad EAS AF: 0.107

Gnomad SAS AF: 0.715

Gnomad FIN AF: 0.379

Gnomad MID AF: 0.272

Gnomad NFE AF: 0.388

Gnomad OTH AF: 0.404

GnomAD3 exomes AF: 0.422 AC: 65568 AN: 155268 Hom.: 15596 AF XY: 0.437 AC XY: 36351 AN XY: 83098

Gnomad AFR exome AF: 0.625

Gnomad AMR exome AF: 0.423

Gnomad ASJ exome AF: 0.317

Gnomad EAS exome AF: 0.107

Gnomad SAS exome AF: 0.693

Gnomad FIN exome AF: 0.380

Gnomad NFE exome AF: 0.378

Gnomad OTH exome AF: 0.403

GnomAD4 exome AF: 0.399 AC: 557487 AN: 1398270 Hom.: 118091 Cov.: 57 AF XY: 0.405 AC XY: 279415 AN XY: 689500

Gnomad4 AFR exome AF: 0.623

Gnomad4 AMR exome AF: 0.419

Gnomad4 ASJ exome AF: 0.322

Gnomad4 EAS exome AF: 0.0954

Gnomad4 SAS exome AF: 0.692

Gnomad4 FIN exome AF: 0.386

Gnomad4 NFE exome AF: 0.383

Gnomad4 OTH exome AF: 0.395

GnomAD4 genome AF: 0.452 AC: 68773 AN: 152140 Hom.: 16795 Cov.: 34 AF XY: 0.454 AC XY: 33729 AN XY: 74372

Gnomad4 AFR AF: 0.617

Gnomad4 AMR AF: 0.423

Gnomad4 ASJ AF: 0.301

Gnomad4 EAS AF: 0.106

Gnomad4 SAS AF: 0.714

Gnomad4 FIN AF: 0.379

Gnomad4 NFE AF: 0.388

Gnomad4 OTH AF: 0.408

Alfa AF: 0.344 Hom.: 2352

Bravo AF: 0.451

TwinsUK AF: 0.387 AC: 1436

ALSPAC AF: 0.382 AC: 1474

ESP6500AA AF: 0.574 AC: 2270

ESP6500EA AF: 0.351 AC: 2881

ExAC AF: 0.359 AC: 38526

Asia WGS AF: 0.469 AC: 1628 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.045
BayesDel_addAF	Benign	-0.62	T
BayesDel_noAF	Benign	-0.52
CADD	Benign	0.15
DANN	Benign	0.69
DEOGEN2	Benign	0.074	T
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.0056	N
LIST_S2	Benign	0.095	T
MetaRNN	Benign	0.0000020	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	0.090	N
MutationTaster	Benign	1.0	P
PrimateAI	Benign	0.39	T
PROVEAN	Benign	0.60	N
REVEL	Benign	0.13
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.0	B
Vest4		0.030
MPC		0.059
ClinPred		0.0019	T
GERP RS		-3.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.037
gMVP		0.20

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: rs7199949; hg19: chr16-31096164; COSMIC: COSV54923846; COSMIC: COSV54923846;