9-33797763-G-A

Position:

• chr9-33797763-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_002771.4(PRSS3):​c.201-66G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.593 in 1,431,260 control chromosomes in the GnomAD database, including 232,146 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.47 (8537 hom., cov: 36)
  • Exomes 𝑓: 0.59 (232146 hom.)
  • Failed GnomAD Quality Control
• Consequence: PRSS3 NM_002771.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.0740

Genes affected

PRSS3 (HGNC:9486): (serine protease 3) This gene encodes a trypsinogen, which is a member of the trypsin family of serine proteases. This enzyme is expressed in the brain and pancreas and is resistant to common trypsin inhibitors. It is active on peptide linkages involving the carboxyl group of lysine or arginine. This gene is localized to the locus of T cell receptor beta variable orphans on chromosome 9. Four transcript variants encoding different isoforms have been described for this gene. [provided by RefSeq, Oct 2010]

UBE2R2-AS1 (HGNC:49911): (UBE2R2 antisense RNA 1)

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 9-33797763-G-A is Benign according to our data. Variant chr9-33797763-G-A is described in ClinVar as [Benign]. Clinvar id is 1237663.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAdExome4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.72 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PRSS3	NM_002771.4	c.201-66G>A		intron_variant		ENST00000379405.4	NP_002762.3
UBE2R2-AS1	NR_170204.1	n.558+605C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PRSS3	ENST00000379405.4	c.201-66G>A		intron_variant		1	NM_002771.4	ENSP00000368715	P1
UBE2R2-AS1	ENST00000705030.1	n.425+605C>T		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.00 AC: 69197 AN: 147264 Hom.: 8539 Cov.: 36 FAILED QC

Gnomad AFR AF: 0.404

Gnomad AMI AF: 0.414

Gnomad AMR AF: 0.502

Gnomad ASJ AF: 0.541

Gnomad EAS AF: 0.713

Gnomad SAS AF: 0.475

Gnomad FIN AF: 0.450

Gnomad MID AF: 0.549

Gnomad NFE AF: 0.483

Gnomad OTH AF: 0.483

GnomAD4 exome AF: 0.593 AC: 849040 AN: 1431260 Hom.: 232146 AF XY: 0.590 AC XY: 420116 AN XY: 712030

Gnomad4 AFR exome AF: 0.477

Gnomad4 AMR exome AF: 0.639

Gnomad4 ASJ exome AF: 0.632

Gnomad4 EAS exome AF: 0.727

Gnomad4 SAS exome AF: 0.507

Gnomad4 FIN exome AF: 0.517

Gnomad4 NFE exome AF: 0.600

Gnomad4 OTH exome AF: 0.587

GnomAD4 genome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.470 AC: 69217 AN: 147374 Hom.: 8537 Cov.: 36 AF XY: 0.468 AC XY: 33711 AN XY: 71978

Gnomad4 AFR AF: 0.404

Gnomad4 AMR AF: 0.501

Gnomad4 ASJ AF: 0.541

Gnomad4 EAS AF: 0.713

Gnomad4 SAS AF: 0.475

Gnomad4 FIN AF: 0.450

Gnomad4 NFE AF: 0.483

Gnomad4 OTH AF: 0.486

Alfa AF: 0.333 Hom.: 401

Bravo AF: 0.606

Asia WGS AF: 0.649 AC: 2252 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Aug 15, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	2.2
DANN	Benign	0.88

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

Other links and lift over

dbSNP: rs83922; hg19: chr9-33797761;