rs1550094

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001195129.2(PRSS56):c.88G>A(p.Ala30Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.694 in 1,530,984 control chromosomes in the GnomAD database, including 371,791 homozygotes. In-silico tool predicts a benign outcome for this variant. 9/13 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.65 ( 32965 hom., cov: 32)

Exomes 𝑓: 0.70 ( 338826 hom. )

Consequence

PRSS56
NM_001195129.2 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 0.922

Publications

38 publications found

Variant links:

Genes affected

PRSS56 (HGNC:39433): (serine protease 56) This gene encodes a protein that contains a peptidase S1 domain and possesses trypsin-like serine protease activity. The encoded protein may play a role in eye development, and mutations in this gene are a cause of autosomal recessive posterior microphthalmos. [provided by RefSeq, Dec 2011]

PRSS56 Gene-Disease associations (from GenCC):

isolated microphthalmia 6
Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: PanelApp Australia, G2P, Labcorp Genetics (formerly Invitae)
nanophthalmia
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

PRSS56 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=5.478455E-7).

BP6

Variant 2-232520686-G-A is Benign according to our data. Variant chr2-232520686-G-A is described in ClinVar as Benign. ClinVar VariationId is 677180.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.879 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRSS56	NM_001195129.2 link	c.88G>A	p.Ala30Thr	missense_variant	Exon 1 of 13	ENST00000617714.2	NP_001182058.1	P0CW18
PRSS56	NM_001369848.1 link	c.88G>A	p.Ala30Thr	missense_variant	Exon 1 of 13		NP_001356777.1
PRSS56	XM_047445431.1 link	c.88G>A	p.Ala30Thr	missense_variant	Exon 1 of 12		XP_047301387.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRSS56	ENST00000617714.2 link	c.88G>A	p.Ala30Thr	missense_variant	Exon 1 of 13	5	NM_001195129.2	ENSP00000479745.1		P0CW18

Frequencies

GnomAD3 genomes

AF:

0.648

AC:

98494

AN:

151898

Hom.:

32938

Cov.:

show subpopulations

Gnomad AFR

AF:

0.484

Gnomad AMI

AF:

0.586

Gnomad AMR

AF:

0.707

Gnomad ASJ

AF:

0.687

Gnomad EAS

AF:

0.901

Gnomad SAS

AF:

0.698

Gnomad FIN

AF:

0.763

Gnomad MID

AF:

0.636

Gnomad NFE

AF:

0.694

Gnomad OTH

AF:

0.622

GnomAD2 exomes

AF:

0.717

AC:

95950

AN:

133744

AF XY:

0.714

show subpopulations

Gnomad AFR exome

AF:

0.470

Gnomad AMR exome

AF:

0.785

Gnomad ASJ exome

AF:

0.699

Gnomad EAS exome

AF:

0.899

Gnomad FIN exome

AF:

0.752

Gnomad NFE exome

AF:

0.695

Gnomad OTH exome

AF:

0.693

GnomAD4 exome

AF:

0.699

AC:

963286

AN:

1378968

Hom.:

338826

Cov.:

AF XY:

0.699

AC XY:

475195

AN XY:

680082

show subpopulations

African (AFR)

AF:

0.472

AC:

14872

AN:

31490

American (AMR)

AF:

0.775

AC:

27623

AN:

35630

Ashkenazi Jewish (ASJ)

AF:

0.696

AC:

17463

AN:

25096

East Asian (EAS)

AF:

0.875

AC:

31187

AN:

35654

South Asian (SAS)

AF:

0.688

AC:

54461

AN:

79102

European-Finnish (FIN)

AF:

0.757

AC:

25631

AN:

33868

Middle Eastern (MID)

AF:

0.620

AC:

3513

AN:

5668

European-Non Finnish (NFE)

AF:

0.697

AC:

748627

AN:

1074770

Other (OTH)

AF:

0.692

AC:

39909

AN:

57690

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.477

Heterozygous variant carriers

13356

26712

40068

53424

66780

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

19250

38500

57750

77000

96250

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.648

AC:

98559

AN:

152016

Hom.:

32965

Cov.:

AF XY:

0.655

AC XY:

48679

AN XY:

74314

show subpopulations

African (AFR)

AF:

0.484

AC:

20065

AN:

41440

American (AMR)

AF:

0.707

AC:

10814

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.687

AC:

2386

AN:

3472

East Asian (EAS)

AF:

0.901

AC:

4645

AN:

5158

South Asian (SAS)

AF:

0.698

AC:

3364

AN:

4818

European-Finnish (FIN)

AF:

0.763

AC:

8075

AN:

10582

Middle Eastern (MID)

AF:

0.636

AC:

187

AN:

294

European-Non Finnish (NFE)

AF:

0.694

AC:

47169

AN:

67942

Other (OTH)

AF:

0.626

AC:

1322

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1698

3396

5095

6793

8491

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

792

1584

2376

3168

3960

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.689

Hom.:

75029

Bravo

AF:

0.640

TwinsUK

AF:

0.706

AC:

2616

ALSPAC

AF:

0.708

AC:

2729

ExAC

AF:

0.609

AC:

10624

Asia WGS

AF:

0.754

AC:

2621

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Isolated microphthalmia 6

Benign:2

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Oct 25, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:2

Mar 22, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.057

BayesDel_addAF

Benign

-0.58

BayesDel_noAF

Benign

-0.46

CADD

Benign

(source)

DANN

Benign

0.88

DEOGEN2

Benign

0.0041

T;T

FATHMM_MKL

Benign

0.049

LIST_S2

Benign

0.18

T;T

MetaRNN

Benign

5.5e-7

T;T

MutationAssessor

Benign

-0.34

.;N

PhyloP100

0.92

PrimateAI

Uncertain

0.51

Sift4G

Benign

1.0

T;T

Vest4

0.029

GERP RS

2.3

PromoterAI

-0.020

Neutral

(source)

Varity_R

0.039

gMVP

0.28

Mutation Taster

=99/1

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over