16-31087690-T-C

Variant names:

• chr16-31087690-T-C
• rs11150606
• NM_001039503.3:c.89A>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.89A>G​(p.Gln30Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.051 in 1,612,712 control chromosomes in the GnomAD database, including 17,080 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 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 0.060 (1886 hom., cov: 33)
  • Exomes 𝑓: 0.050 (15194 hom.)
• Consequence: PRSS53 NM_001039503.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.64
• Publications: 40 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=1.1534233E-6).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.768 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRSS53	NM_001039503.3	MANE Select	c.89A>G	p.Gln30Arg	missense	Exon 3 of 11	NP_001034592.1	Q2L4Q9

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRSS53	ENST00000280606.7	TSL:1 MANE Select	c.89A>G	p.Gln30Arg	missense	Exon 3 of 11	ENSP00000280606.6	Q2L4Q9
	ENSG00000255439	ENST00000529564.1	TSL:4	c.314A>G	p.Gln105Arg	missense	Exon 4 of 5	ENSP00000431371.1	E9PLN8
	ENSG00000255439	ENST00000533518.5	TSL:1	n.*73A>G		non_coding_transcript_exon	Exon 5 of 13	ENSP00000433035.1	H0YD56

Frequencies

GnomAD3 genomes AF: 0.0600 AC: 9130 AN: 152170 Hom.: 1885 Cov.: 33

Gnomad AFR AF: 0.0110

Gnomad AMI AF: 0.00548

Gnomad AMR AF: 0.144

Gnomad ASJ AF: 0.0138

Gnomad EAS AF: 0.788

Gnomad SAS AF: 0.0341

Gnomad FIN AF: 0.0789

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.0178

Gnomad OTH AF: 0.0660

GnomAD2 exomes AF: 0.118 AC: 28877 AN: 245378 AF XY: 0.102

Gnomad AFR exome AF: 0.0107

Gnomad AMR exome AF: 0.284

Gnomad ASJ exome AF: 0.0113

Gnomad EAS exome AF: 0.797

Gnomad FIN exome AF: 0.0777

Gnomad NFE exome AF: 0.0192

Gnomad OTH exome AF: 0.0798

GnomAD4 exome AF: 0.0501 AC: 73103 AN: 1460424 Hom.: 15194 Cov.: 32 AF XY: 0.0478 AC XY: 34687 AN XY: 726398

African (AFR) AF: 0.00661 AC: 221 AN: 33452

American (AMR) AF: 0.271 AC: 12037 AN: 44346

Ashkenazi Jewish (ASJ) AF: 0.0111 AC: 291 AN: 26118

East Asian (EAS) AF: 0.789 AC: 31207 AN: 39574

South Asian (SAS) AF: 0.0210 AC: 1808 AN: 85906

European-Finnish (FIN) AF: 0.0776 AC: 4138 AN: 53322

Middle Eastern (MID) AF: 0.0118 AC: 68 AN: 5768

European-Non Finnish (NFE) AF: 0.0172 AC: 19171 AN: 1111618

Other (OTH) AF: 0.0690 AC: 4162 AN: 60320

GnomAD4 genome AF: 0.0600 AC: 9131 AN: 152288 Hom.: 1886 Cov.: 33 AF XY: 0.0664 AC XY: 4944 AN XY: 74470

African (AFR) AF: 0.0109 AC: 455 AN: 41580

American (AMR) AF: 0.144 AC: 2207 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.0138 AC: 48 AN: 3472

East Asian (EAS) AF: 0.788 AC: 4062 AN: 5156

South Asian (SAS) AF: 0.0333 AC: 161 AN: 4830

European-Finnish (FIN) AF: 0.0789 AC: 838 AN: 10616

Middle Eastern (MID) AF: 0.0102 AC: 3 AN: 294

European-Non Finnish (NFE) AF: 0.0178 AC: 1213 AN: 68012

Other (OTH) AF: 0.0658 AC: 139 AN: 2112

Alfa AF: 0.0390 Hom.: 3930

Bravo AF: 0.0729

TwinsUK AF: 0.0129 AC: 48

ALSPAC AF: 0.0174 AC: 67

ESP6500AA AF: 0.0127 AC: 52

ESP6500EA AF: 0.0176 AC: 147

ExAC AF: 0.106 AC: 12811

Asia WGS AF: 0.326 AC: 1130 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.072
BayesDel_addAF	Benign	-0.50	T
BayesDel_noAF	Benign	-0.35
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.0075	T
Eigen	Benign	-0.39
Eigen_PC	Benign	-0.12
FATHMM_MKL	Benign	0.68	D
LIST_S2	Benign	0.71	T
MetaRNN	Benign	0.0000012	T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	-0.19	N
PhyloP100		1.6
PrimateAI	Benign	0.40	T
PROVEAN	Benign	0.32	N
REVEL	Benign	0.19
Sift	Benign	0.44	T
Sift4G	Benign	0.12	T
Polyphen		0.14	B
Vest4		0.17
MPC		0.27
ClinPred		0.014	T
GERP RS		6.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.064
gMVP		0.38
Mutation Taster		=90/10	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs11150606; hg19: chr16-31099011; COSMIC: COSV54924707; COSMIC: COSV54924707;