9-33750750-G-T

Variant summary

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

The ENST00000342836.9(PRSS3):c.-53+23G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.364 in 1,415,278 control chromosomes in the GnomAD database, including 96,576 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.31 (8385 hom., cov: 31)
  • Exomes 𝑓: 0.37 (88191 hom.)
• Consequence: PRSS3 ENST00000342836.9 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.298

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 9-33750750-G-T is Benign according to our data. Variant chr9-33750750-G-T is described in ClinVar as [Benign]. Clinvar id is 1280871.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.542 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
UBE2R2-AS1	NR_170204.1	n.559-12334C>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PRSS3	ENST00000342836.9	c.-53+23G>T		intron_variant		1
PRSS3	ENST00000361005.10	c.-285+23G>T		intron_variant		1
UBE2R2-AS1	ENST00000705030.1	n.644-12334C>A		intron_variant, non_coding_transcript_variant
PRSS3	ENST00000468152.2	n.49+23G>T		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.313 AC: 47530 AN: 151738 Hom.: 8388 Cov.: 31

Gnomad AFR AF: 0.151

Gnomad AMI AF: 0.304

Gnomad AMR AF: 0.389

Gnomad ASJ AF: 0.389

Gnomad EAS AF: 0.560

Gnomad SAS AF: 0.351

Gnomad FIN AF: 0.295

Gnomad MID AF: 0.367

Gnomad NFE AF: 0.371

Gnomad OTH AF: 0.349

GnomAD3 exomes AF: 0.348 AC: 11505 AN: 33048 Hom.: 2161 AF XY: 0.349 AC XY: 6121 AN XY: 17552

Gnomad AFR exome AF: 0.101

Gnomad AMR exome AF: 0.369

Gnomad ASJ exome AF: 0.371

Gnomad EAS exome AF: 0.526

Gnomad SAS exome AF: 0.348

Gnomad FIN exome AF: 0.275

Gnomad NFE exome AF: 0.343

Gnomad OTH exome AF: 0.345

GnomAD4 exome AF: 0.370 AC: 467620 AN: 1263422 Hom.: 88191 Cov.: 64 AF XY: 0.370 AC XY: 226862 AN XY: 612828

Gnomad4 AFR exome AF: 0.131

Gnomad4 AMR exome AF: 0.378

Gnomad4 ASJ exome AF: 0.385

Gnomad4 EAS exome AF: 0.524

Gnomad4 SAS exome AF: 0.357

Gnomad4 FIN exome AF: 0.290

Gnomad4 NFE exome AF: 0.375

Gnomad4 OTH exome AF: 0.365

GnomAD4 genome AF: 0.313 AC: 47528 AN: 151856 Hom.: 8385 Cov.: 31 AF XY: 0.313 AC XY: 23248 AN XY: 74206

Gnomad4 AFR AF: 0.151

Gnomad4 AMR AF: 0.389

Gnomad4 ASJ AF: 0.389

Gnomad4 EAS AF: 0.559

Gnomad4 SAS AF: 0.351

Gnomad4 FIN AF: 0.295

Gnomad4 NFE AF: 0.371

Gnomad4 OTH AF: 0.349

Alfa AF: 0.220 Hom.: 629

Bravo AF: 0.317

Asia WGS AF: 0.419 AC: 1455 AN: 3476

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 14, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
Cadd	Benign	8.4
Dann	Benign	0.75

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs10971678; hg19: chr9-33750748; COSMIC: COSV61559558; COSMIC: COSV61559558;