2-232521438-C-G

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_001195129.2(PRSS56):c.205+10C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00273 in 1,532,842 control chromosomes in the GnomAD database, including 185 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0035 (21 hom., cov: 33)
  • Exomes 𝑓: 0.0026 (164 hom.)
• Consequence: PRSS56 NM_001195129.2 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.0420

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]

ACMG classification

Verdict is Benign. Variant got -16 ACMG points.

• BP6: Variant 2-232521438-C-G is Benign according to our data. Variant chr2-232521438-C-G is described in ClinVar as [Benign]. Clinvar id is 707140.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0877 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PRSS56	NM_001195129.2	c.205+10C>G		intron_variant		ENST00000617714.2
PRSS56	NM_001369848.1	c.205+10C>G		intron_variant
PRSS56	XM_047445431.1	c.205+10C>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PRSS56	ENST00000617714.2	c.205+10C>G		intron_variant		5	NM_001195129.2	P1

Frequencies

GnomAD3 genomes AF: 0.00352 AC: 536 AN: 152184 Hom.: 21 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000196

Gnomad ASJ AF: 0.000864

Gnomad EAS AF: 0.0942

Gnomad SAS AF: 0.00665

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000882

Gnomad OTH AF: 0.00143

GnomAD3 exomes AF: 0.00772 AC: 1037 AN: 134362 Hom.: 45 AF XY: 0.00760 AC XY: 556 AN XY: 73186

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000822

Gnomad ASJ exome AF: 0.000241

Gnomad EAS exome AF: 0.0919

Gnomad SAS exome AF: 0.00240

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000189

Gnomad OTH exome AF: 0.00313

GnomAD4 exome AF: 0.00265 AC: 3654 AN: 1380540 Hom.: 164 Cov.: 30 AF XY: 0.00273 AC XY: 1860 AN XY: 681494

Gnomad4 AFR exome AF: 0.0000317

Gnomad4 AMR exome AF: 0.0000560

Gnomad4 ASJ exome AF: 0.000596

Gnomad4 EAS exome AF: 0.0888

Gnomad4 SAS exome AF: 0.00278

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000483

Gnomad4 OTH exome AF: 0.00331

GnomAD4 genome AF: 0.00353 AC: 538 AN: 152302 Hom.: 21 Cov.: 33 AF XY: 0.00432 AC XY: 322 AN XY: 74454

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.000196

Gnomad4 ASJ AF: 0.000864

Gnomad4 EAS AF: 0.0946

Gnomad4 SAS AF: 0.00686

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000882

Gnomad4 OTH AF: 0.00142

Alfa AF: 0.000812 Hom.: 0

Bravo AF: 0.00420

Asia WGS AF: 0.0240 AC: 82 AN: 3474

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Isolated microphthalmia 6 Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 26, 2024

- -

PRSS56-related disorder Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Sep 10, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 14, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
Cadd	Benign	8.5
Dann	Benign	0.77

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.25		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.25		Position offset: 16

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs77311538; hg19: chr2-233386148;