chr16-31084843-G-C

Variant names:

• chr16-31084843-G-C
• rs7199949
• NM_001039503.3:c.1216C>G

Variant summary

Our verdict is Benign. The variant received -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. 16/21 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
• Publications: 41 publications found

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]

ENSG00000255439 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001039503.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRSS53	NM_001039503.3	MANE Select	c.1216C>G	p.Pro406Ala	missense	Exon 8 of 11	NP_001034592.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRSS53	ENST00000280606.7	TSL:1 MANE Select	c.1216C>G	p.Pro406Ala	missense	Exon 8 of 11	ENSP00000280606.6
	ENSG00000255439	ENST00000533518.5	TSL:1	n.*1200C>G		non_coding_transcript_exon	Exon 10 of 13	ENSP00000433035.1
	ENSG00000255439	ENST00000533518.5	TSL:1	n.*1200C>G		3_prime_UTR	Exon 10 of 13	ENSP00000433035.1

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

GnomAD2 exomes AF: 0.422 AC: 65568 AN: 155268 AF XY: 0.437

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 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

African (AFR) AF: 0.623 AC: 19844 AN: 31828

American (AMR) AF: 0.419 AC: 15037 AN: 35872

Ashkenazi Jewish (ASJ) AF: 0.322 AC: 7991 AN: 24800

East Asian (EAS) AF: 0.0954 AC: 3439 AN: 36036

South Asian (SAS) AF: 0.692 AC: 54609 AN: 78950

European-Finnish (FIN) AF: 0.386 AC: 18821 AN: 48776

Middle Eastern (MID) AF: 0.318 AC: 1782 AN: 5604

European-Non Finnish (NFE) AF: 0.383 AC: 413114 AN: 1078528

Other (OTH) AF: 0.395 AC: 22850 AN: 57876

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

African (AFR) AF: 0.617 AC: 25622 AN: 41510

American (AMR) AF: 0.423 AC: 6465 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.301 AC: 1044 AN: 3472

East Asian (EAS) AF: 0.106 AC: 550 AN: 5178

South Asian (SAS) AF: 0.714 AC: 3443 AN: 4822

European-Finnish (FIN) AF: 0.379 AC: 4010 AN: 10592

Middle Eastern (MID) AF: 0.265 AC: 78 AN: 294

European-Non Finnish (NFE) AF: 0.388 AC: 26363 AN: 67962

Other (OTH) AF: 0.408 AC: 862 AN: 2112

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 v4.9

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
PhyloP100		-0.41
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
Mutation Taster		=100/0	polymorphism (auto)

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