9-33796914-A-G

Variant summary

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

The NM_002771.4(PRSS3):c.200+112A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.96 in 151,580 control chromosomes in the GnomAD database, including 69,883 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.96 (69883 hom., cov: 31)
  • Exomes 𝑓: 0.99 (686750 hom.)
  • Failed GnomAD Quality Control
• Consequence: PRSS3 NM_002771.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.925

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=-0.96).
• BP6: Variant 9-33796914-A-G is Benign according to our data. Variant chr9-33796914-A-G is described in ClinVar as [Benign]. Clinvar id is 1291262.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.99 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PRSS3	NM_002771.4	c.200+112A>G		intron_variant		ENST00000379405.4
UBE2R2-AS1	NR_170204.1	n.558+1454T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PRSS3	ENST00000379405.4	c.200+112A>G		intron_variant		1	NM_002771.4	P1
UBE2R2-AS1	ENST00000705030.1	n.425+1454T>C		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.960 AC: 145409 AN: 151470 Hom.: 69838 Cov.: 31

Gnomad AFR AF: 0.901

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.960

Gnomad ASJ AF: 0.992

Gnomad EAS AF: 0.911

Gnomad SAS AF: 0.972

Gnomad FIN AF: 0.958

Gnomad MID AF: 0.990

Gnomad NFE AF: 0.996

Gnomad OTH AF: 0.975

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.987 AC: 1391056 AN: 1409588 Hom.: 686750 AF XY: 0.987 AC XY: 693518 AN XY: 702798

Gnomad4 AFR exome AF: 0.897

Gnomad4 AMR exome AF: 0.958

Gnomad4 ASJ exome AF: 0.989

Gnomad4 EAS exome AF: 0.867

Gnomad4 SAS exome AF: 0.978

Gnomad4 FIN exome AF: 0.959

Gnomad4 NFE exome AF: 0.997

Gnomad4 OTH exome AF: 0.981

GnomAD4 genome AF: 0.960 AC: 145509 AN: 151580 Hom.: 69883 Cov.: 31 AF XY: 0.958 AC XY: 70975 AN XY: 74090

Gnomad4 AFR AF: 0.901

Gnomad4 AMR AF: 0.960

Gnomad4 ASJ AF: 0.992

Gnomad4 EAS AF: 0.910

Gnomad4 SAS AF: 0.972

Gnomad4 FIN AF: 0.958

Gnomad4 NFE AF: 0.996

Gnomad4 OTH AF: 0.975

Alfa AF: 0.926 Hom.: 7119

Bravo AF: 0.958

Asia WGS AF: 0.922 AC: 3206 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

Aug 15, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
Cadd	Benign	0.55
Dann	Benign	0.69

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: rs855580; hg19: chr9-33796912; COSMIC: COSV61560685; COSMIC: COSV61560685;