dbSNP rs79872260: PRSS56:c.98-143C>T (chr2-232521178-C-T) – ACMG Classification: Benign (-20 pts)

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.98-143C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00761 in 637,768 control chromosomes in the GnomAD database, including 156 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.022 ( 117 hom., cov: 33)

Exomes 𝑓: 0.0032 ( 39 hom. )

Consequence

PRSS56
NM_001195129.2 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.171

Publications

0 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: 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 (BayesDel_noAF=-0.81).

BP6

Variant 2-232521178-C-T is Benign according to our data. Variant chr2-232521178-C-T is described in ClinVar as Benign. ClinVar VariationId is 1182160.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0717 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001195129.2. 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
	PRSS56	NM_001195129.2	MANE Select	c.98-143C>T		intron	N/A	NP_001182058.1	P0CW18
	PRSS56	NM_001369848.1		c.98-143C>T		intron	N/A	NP_001356777.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRSS56	ENST00000617714.2	TSL:5 MANE Select	c.98-143C>T		intron	N/A	ENSP00000479745.1	P0CW18

Frequencies

GnomAD3 genomes

AF:

0.0215

AC:

3278

AN:

152200

Hom.:

120

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0740

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00720

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00310

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000588

Gnomad OTH

AF:

0.0215

GnomAD4 exome

AF:

0.00324

AC:

1573

AN:

485450

Hom.:

AF XY:

0.00285

AC XY:

725

AN XY:

254512

show subpopulations

African (AFR)

AF:

0.0772

AC:

1064

AN:

13790

American (AMR)

AF:

0.00406

AC:

AN:

23918

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

14722

East Asian (EAS)

AF:

0.00

AC:

AN:

31252

South Asian (SAS)

AF:

0.00202

AC:

AN:

47950

European-Finnish (FIN)

AF:

0.00

AC:

AN:

30090

Middle Eastern (MID)

AF:

0.00667

AC:

AN:

2098

European-Non Finnish (NFE)

AF:

0.000500

AC:

147

AN:

294260

Other (OTH)

AF:

0.00563

AC:

154

AN:

27370

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

143

215

286

358

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

100

<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:

0.0215

AC:

3281

AN:

152318

Hom.:

117

Cov.:

AF XY:

0.0205

AC XY:

1525

AN XY:

74498

show subpopulations

African (AFR)

AF:

0.0739

AC:

3071

AN:

41572

American (AMR)

AF:

0.00719

AC:

110

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5178

South Asian (SAS)

AF:

0.00290

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10624

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000588

AC:

AN:

68020

Other (OTH)

AF:

0.0213

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

162

325

487

650

812

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

102

136

170

<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:

0.0161

Hom.:

Bravo

AF:

0.0248

Asia WGS

AF:

0.00520

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

7.4

(source)

DANN

Benign

0.74

PhyloP100

0.17

Mutation Taster

=100/0

polymorphism

(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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over