2-232521258-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001195129.2(PRSS56):c.98-63C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0968 in 1,328,056 control chromosomes in the GnomAD database, including 6,718 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.087 (619 hom., cov: 33)
  • Exomes 𝑓: 0.098 (6099 hom.)
• Consequence: PRSS56 NM_001195129.2 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.972

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 2-232521258-C-T is Benign according to our data. Variant chr2-232521258-C-T is described in ClinVar as [Benign]. Clinvar id is 1282125.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.104 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PRSS56	NM_001195129.2	c.98-63C>T		intron_variant		ENST00000617714.2
PRSS56	NM_001369848.1	c.98-63C>T		intron_variant
PRSS56	XM_047445431.1	c.98-63C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PRSS56	ENST00000617714.2	c.98-63C>T		intron_variant		5	NM_001195129.2	P1

Frequencies

GnomAD3 genomes AF: 0.0870 AC: 13233 AN: 152152 Hom.: 619 Cov.: 33

Gnomad AFR AF: 0.0679

Gnomad AMI AF: 0.201

Gnomad AMR AF: 0.0781

Gnomad ASJ AF: 0.132

Gnomad EAS AF: 0.00846

Gnomad SAS AF: 0.0885

Gnomad FIN AF: 0.0609

Gnomad MID AF: 0.150

Gnomad NFE AF: 0.106

Gnomad OTH AF: 0.101

GnomAD4 exome AF: 0.0980 AC: 115281 AN: 1175786 Hom.: 6099 AF XY: 0.0986 AC XY: 57941 AN XY: 587556

Gnomad4 AFR exome AF: 0.0680

Gnomad4 AMR exome AF: 0.0603

Gnomad4 ASJ exome AF: 0.128

Gnomad4 EAS exome AF: 0.0169

Gnomad4 SAS exome AF: 0.0909

Gnomad4 FIN exome AF: 0.0701

Gnomad4 NFE exome AF: 0.104

Gnomad4 OTH exome AF: 0.0971

GnomAD4 genome AF: 0.0870 AC: 13244 AN: 152270 Hom.: 619 Cov.: 33 AF XY: 0.0844 AC XY: 6285 AN XY: 74464

Gnomad4 AFR AF: 0.0681

Gnomad4 AMR AF: 0.0779

Gnomad4 ASJ AF: 0.132

Gnomad4 EAS AF: 0.00848

Gnomad4 SAS AF: 0.0883

Gnomad4 FIN AF: 0.0609

Gnomad4 NFE AF: 0.106

Gnomad4 OTH AF: 0.100

Alfa AF: 0.0915 Hom.: 79

Bravo AF: 0.0879

Asia WGS AF: 0.0560 AC: 196 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 26, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
Cadd	Benign	7.3
Dann	Benign	0.74

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs62193795; hg19: chr2-233385968;