NM_002771.4:c.201-66G>A

Variant names:

• chr9-33797763-G-A
• rs83922
• NM_002771.4:c.201-66G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 4 publications found

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

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002771.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRSS3	NM_002771.4	MANE Select	c.201-66G>A		intron	N/A	NP_002762.3
	PRSS3	NM_001197097.3		c.243-66G>A		intron	N/A	NP_001184026.3	P35030-4
	PRSS3	NM_001197098.1		c.180-66G>A		intron	N/A	NP_001184027.1	P35030

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRSS3	ENST00000379405.4	TSL:1 MANE Select	c.201-66G>A		intron	N/A	ENSP00000368715.3	P35030-3
	PRSS3	ENST00000342836.9	TSL:1	c.237-66G>A		intron	N/A	ENSP00000340889.5	A0A7P0MNE9
	PRSS3	ENST00000429677.8	TSL:1	c.180-66G>A		intron	N/A	ENSP00000401828.3	P35030-5

Frequencies

GnomAD3 genomes AF: 0.470 AC: 69197 AN: 147264 Hom.: 8539 Cov.: 36

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

African (AFR) AF: 0.477 AC: 15435 AN: 32388

American (AMR) AF: 0.639 AC: 27887 AN: 43668

Ashkenazi Jewish (ASJ) AF: 0.632 AC: 16078 AN: 25456

East Asian (EAS) AF: 0.727 AC: 28300 AN: 38948

South Asian (SAS) AF: 0.507 AC: 42812 AN: 84370

European-Finnish (FIN) AF: 0.517 AC: 26075 AN: 50470

Middle Eastern (MID) AF: 0.609 AC: 3399 AN: 5584

European-Non Finnish (NFE) AF: 0.600 AC: 654388 AN: 1091312

Other (OTH) AF: 0.587 AC: 34666 AN: 59064

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

African (AFR) AF: 0.404 AC: 16110 AN: 39924

American (AMR) AF: 0.501 AC: 7445 AN: 14854

Ashkenazi Jewish (ASJ) AF: 0.541 AC: 1811 AN: 3346

East Asian (EAS) AF: 0.713 AC: 3591 AN: 5036

South Asian (SAS) AF: 0.475 AC: 2206 AN: 4648

European-Finnish (FIN) AF: 0.450 AC: 4616 AN: 10262

Middle Eastern (MID) AF: 0.549 AC: 156 AN: 284

European-Non Finnish (NFE) AF: 0.483 AC: 31925 AN: 66096

Other (OTH) AF: 0.486 AC: 990 AN: 2038

Alfa AF: 0.333 Hom.: 401

Bravo AF: 0.606

Asia WGS AF: 0.649 AC: 2252 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	2.2
DANN	Benign	0.88
PhyloP100		-0.074
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs83922; hg19: chr9-33797761;