9-33797763-G-T

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 2P and 10B. PM2 BP4_Strong BP6_Moderate BS1

The NM_002771.4(PRSS3):c.201-66G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0027 in 1,486,938 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.027 (0 hom., cov: 36)
  • Exomes 𝑓: 0.00058 (0 hom.)
• Consequence: PRSS3 NM_002771.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• 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 -8 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 9-33797763-G-T is Benign according to our data. Variant chr9-33797763-G-T is described in ClinVar as [Benign]. Clinvar id is 1245449.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0267 (3213/120268) while in subpopulation AFR AF= 0.0425 (1331/31342). AF 95% confidence interval is 0.0406. There are 0 homozygotes in gnomad4. There are 1709 alleles in male gnomad4 subpopulation. Median coverage is 36. This position pass quality control queck.

Transcripts

RefSeq

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

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.0266 AC: 3201 AN: 120194 Hom.: 0 Cov.: 36

Gnomad AFR AF: 0.0422

Gnomad AMI AF: 0.0180

Gnomad AMR AF: 0.0258

Gnomad ASJ AF: 0.0163

Gnomad EAS AF: 0.00709

Gnomad SAS AF: 0.0109

Gnomad FIN AF: 0.0418

Gnomad MID AF: 0.0254

Gnomad NFE AF: 0.0190

Gnomad OTH AF: 0.0286

GnomAD4 exome AF: 0.000584 AC: 798 AN: 1366670 Hom.: 0 AF XY: 0.000620 AC XY: 421 AN XY: 679274

Gnomad4 AFR exome AF: 0.00197

Gnomad4 AMR exome AF: 0.000758

Gnomad4 ASJ exome AF: 0.00139

Gnomad4 EAS exome AF: 0.000381

Gnomad4 SAS exome AF: 0.0000121

Gnomad4 FIN exome AF: 0.00191

Gnomad4 NFE exome AF: 0.000474

Gnomad4 OTH exome AF: 0.00114

GnomAD4 genome AF: 0.0267 AC: 3213 AN: 120268 Hom.: 0 Cov.: 36 AF XY: 0.0291 AC XY: 1709 AN XY: 58772

Gnomad4 AFR AF: 0.0425

Gnomad4 AMR AF: 0.0258

Gnomad4 ASJ AF: 0.0163

Gnomad4 EAS AF: 0.00733

Gnomad4 SAS AF: 0.0109

Gnomad4 FIN AF: 0.0418

Gnomad4 NFE AF: 0.0190

Gnomad4 OTH AF: 0.0276

Alfa AF: 0.283 Hom.: 401

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

Aug 15, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
Cadd	Benign	2.1
Dann	Benign	0.86

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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;