11-86807809-G-A

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_007173.6(PRSS23):c.166G>A(p.Glu56Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00557 in 1,614,100 control chromosomes in the GnomAD database, including 37 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0039 (3 hom., cov: 32)
  • Exomes 𝑓: 0.0057 (34 hom.)
• Consequence: PRSS23 NM_007173.6 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.927

Genes affected

PRSS23 (HGNC:14370): (serine protease 23) This gene encodes a conserved member of the trypsin family of serine proteases. Mouse studies found a decrease of mRNA levels of this gene after ovulation was induced. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jun 2014]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0061273575).
• BP6: Variant 11-86807809-G-A is Benign according to our data. Variant chr11-86807809-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2642256.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PRSS23	NM_007173.6	c.166G>A	p.Glu56Lys	missense_variant	2/2	ENST00000280258.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PRSS23	ENST00000280258.6	c.166G>A	p.Glu56Lys	missense_variant	2/2	1	NM_007173.6	P1

Frequencies

GnomAD3 genomes AF: 0.00395 AC: 601 AN: 152108 Hom.: 3 Cov.: 32

Gnomad AFR AF: 0.000966

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00183

Gnomad ASJ AF: 0.00461

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00274

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00700

Gnomad OTH AF: 0.00574

GnomAD3 exomes AF: 0.00433 AC: 1089 AN: 251446 Hom.: 4 AF XY: 0.00441 AC XY: 599 AN XY: 135896

Gnomad AFR exome AF: 0.00111

Gnomad AMR exome AF: 0.00121

Gnomad ASJ exome AF: 0.00407

Gnomad EAS exome AF: 0.0000544

Gnomad SAS exome AF: 0.000327

Gnomad FIN exome AF: 0.00383

Gnomad NFE exome AF: 0.00761

Gnomad OTH exome AF: 0.00456

GnomAD4 exome AF: 0.00573 AC: 8383 AN: 1461874 Hom.: 34 Cov.: 31 AF XY: 0.00555 AC XY: 4037 AN XY: 727238

Gnomad4 AFR exome AF: 0.00111

Gnomad4 AMR exome AF: 0.00141

Gnomad4 ASJ exome AF: 0.00467

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.000313

Gnomad4 FIN exome AF: 0.00526

Gnomad4 NFE exome AF: 0.00679

Gnomad4 OTH exome AF: 0.00477

GnomAD4 genome AF: 0.00395 AC: 601 AN: 152226 Hom.: 3 Cov.: 32 AF XY: 0.00366 AC XY: 272 AN XY: 74404

Gnomad4 AFR AF: 0.000963

Gnomad4 AMR AF: 0.00183

Gnomad4 ASJ AF: 0.00461

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00274

Gnomad4 NFE AF: 0.00700

Gnomad4 OTH AF: 0.00568

Alfa AF: 0.00621 Hom.: 8

Bravo AF: 0.00389

TwinsUK AF: 0.00782 AC: 29

ALSPAC AF: 0.00752 AC: 29

ESP6500AA AF: 0.00136 AC: 6

ESP6500EA AF: 0.00663 AC: 57

ExAC AF: 0.00513 AC: 623

Asia WGS AF: 0.000577 AC: 2 AN: 3478

EpiCase AF: 0.00785

EpiControl AF: 0.00729

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Aug 01, 2023

PRSS23: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.062
BayesDel_addAF	Benign	-0.43	T
BayesDel_noAF	Benign	-0.38
Cadd	Benign	2.7
Dann	Benign	0.94
DEOGEN2	Benign	0.018	T;T
Eigen	Benign	-0.76
Eigen_PC	Benign	-0.69
FATHMM_MKL	Benign	0.58	D
LIST_S2	Benign	0.81	T;T
M_CAP	Benign	0.0049	T
MetaRNN	Benign	0.0061	T;T
MetaSVM	Benign	-1.1	T
MutationTaster	Benign	0.98	D;D;N
PrimateAI	Benign	0.35	T
PROVEAN	Benign	-1.2	N;N
REVEL	Benign	0.10
Sift	Benign	0.30	T;T
Sift4G	Benign	0.24	T;T
Polyphen		0.0010	.;B
Vest4		0.080
MVP		0.29
MPC		0.21
ClinPred		0.0023	T
GERP RS		1.9
Varity_R		0.052
gMVP		0.42

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: rs143933691; hg19: chr11-86518851; COSMIC: COSV99722500;