Genetic Variant PRSS56:c.97+27C>T (chr2-232520722-C-T) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001195129.2(PRSS56):c.97+27C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0636 in 1,463,488 control chromosomes in the GnomAD database, including 3,161 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.053 ( 261 hom., cov: 33)

Exomes 𝑓: 0.065 ( 2900 hom. )

Consequence

PRSS56
NM_001195129.2 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: 3.48

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BP6

Variant 2-232520722-C-T is Benign according to our data. Variant chr2-232520722-C-T is described in ClinVar as [Benign]. Clinvar id is 1235033.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0865 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
PRSS56	NM_001195129.2 link	c.97+27C>T	intron_variant	Intron 1 of 12	ENST00000617714.2	NP_001182058.1	P0CW18
PRSS56	NM_001369848.1 link	c.97+27C>T	intron_variant	Intron 1 of 12		NP_001356777.1
PRSS56	XM_047445431.1 link	c.97+27C>T	intron_variant	Intron 1 of 11		XP_047301387.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRSS56	ENST00000617714.2 link	c.97+27C>T		intron_variant	Intron 1 of 12	5	NM_001195129.2	ENSP00000479745.1		P0CW18

Frequencies

GnomAD3 genomes

AF:

0.0530

AC:

8058

AN:

152080

Hom.:

261

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0162

Gnomad AMI

AF:

0.121

Gnomad AMR

AF:

0.0906

Gnomad ASJ

AF:

0.0519

Gnomad EAS

AF:

0.0666

Gnomad SAS

AF:

0.0523

Gnomad FIN

AF:

0.0589

Gnomad MID

AF:

0.0665

Gnomad NFE

AF:

0.0643

Gnomad OTH

AF:

0.0488

GnomAD3 exomes

AF:

0.0657

AC:

8377

AN:

127558

Hom.:

314

AF XY:

0.0642

AC XY:

4449

AN XY:

69256

show subpopulations

Gnomad AFR exome

AF:

0.0143

Gnomad AMR exome

AF:

0.0931

Gnomad ASJ exome

AF:

0.0490

Gnomad EAS exome

AF:

0.0669

Gnomad SAS exome

AF:

0.0571

Gnomad FIN exome

AF:

0.0572

Gnomad NFE exome

AF:

0.0663

Gnomad OTH exome

AF:

0.0627

GnomAD4 exome

AF:

0.0648

AC:

84981

AN:

1311290

Hom.:

2900

Cov.:

AF XY:

0.0644

AC XY:

41553

AN XY:

645682

show subpopulations

Gnomad4 AFR exome

AF:

0.0132

Gnomad4 AMR exome

AF:

0.0903

Gnomad4 ASJ exome

AF:

0.0503

Gnomad4 EAS exome

AF:

0.0625

Gnomad4 SAS exome

AF:

0.0566

Gnomad4 FIN exome

AF:

0.0613

Gnomad4 NFE exome

AF:

0.0668

Gnomad4 OTH exome

AF:

0.0621

GnomAD4 genome

AF:

0.0529

AC:

8054

AN:

152198

Hom.:

261

Cov.:

AF XY:

0.0540

AC XY:

4019

AN XY:

74416

show subpopulations

Gnomad4 AFR

AF:

0.0162

Gnomad4 AMR

AF:

0.0905

Gnomad4 ASJ

AF:

0.0519

Gnomad4 EAS

AF:

0.0663

Gnomad4 SAS

AF:

0.0519

Gnomad4 FIN

AF:

0.0589

Gnomad4 NFE

AF:

0.0643

Gnomad4 OTH

AF:

0.0478

Alfa

AF:

0.0383

Hom.:

Bravo

AF:

0.0534

Asia WGS

AF:

0.0590

AC:

208

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jul 10, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

DANN

Benign

0.58

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over