9-33798840-T-C

Position:

• chr9-33798840-T-C

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.592-188T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0742 in 1,038,770 control chromosomes in the GnomAD database, including 3,473 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.061 (390 hom., cov: 32)
  • Exomes 𝑓: 0.076 (3083 hom.)
• Consequence: PRSS3 NM_002771.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.02

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=-0.89).
• BP6: Variant 9-33798840-T-C is Benign according to our data. Variant chr9-33798840-T-C is described in ClinVar as [Benign]. Clinvar id is 1239378.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0891 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PRSS3	NM_002771.4	c.592-188T>C		intron_variant		ENST00000379405.4	NP_002762.3
UBE2R2-AS1	NR_170204.1	n.374-288A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PRSS3	ENST00000379405.4	c.592-188T>C		intron_variant		1	NM_002771.4	ENSP00000368715	P1
UBE2R2-AS1	ENST00000705030.1	n.236-283A>G		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.0608 AC: 9243 AN: 151910 Hom.: 390 Cov.: 32

Gnomad AFR AF: 0.0144

Gnomad AMI AF: 0.107

Gnomad AMR AF: 0.0414

Gnomad ASJ AF: 0.0409

Gnomad EAS AF: 0.00501

Gnomad SAS AF: 0.0446

Gnomad FIN AF: 0.116

Gnomad MID AF: 0.0348

Gnomad NFE AF: 0.0910

Gnomad OTH AF: 0.0542

GnomAD4 exome AF: 0.0765 AC: 67834 AN: 886742 Hom.: 3083 Cov.: 12 AF XY: 0.0748 AC XY: 33685 AN XY: 450132

Gnomad4 AFR exome AF: 0.0132

Gnomad4 AMR exome AF: 0.0341

Gnomad4 ASJ exome AF: 0.0403

Gnomad4 EAS exome AF: 0.00327

Gnomad4 SAS exome AF: 0.0454

Gnomad4 FIN exome AF: 0.108

Gnomad4 NFE exome AF: 0.0867

Gnomad4 OTH exome AF: 0.0659

GnomAD4 genome AF: 0.0608 AC: 9239 AN: 152028 Hom.: 390 Cov.: 32 AF XY: 0.0609 AC XY: 4523 AN XY: 74326

Gnomad4 AFR AF: 0.0143

Gnomad4 AMR AF: 0.0413

Gnomad4 ASJ AF: 0.0409

Gnomad4 EAS AF: 0.00483

Gnomad4 SAS AF: 0.0440

Gnomad4 FIN AF: 0.116

Gnomad4 NFE AF: 0.0910

Gnomad4 OTH AF: 0.0546

Alfa AF: 0.0786 Hom.: 107

Bravo AF: 0.0511

Asia WGS AF: 0.0220 AC: 76 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	-0.89
CADD	Benign	4.8
DANN	Benign	0.23

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: rs41315997; hg19: chr9-33798838;