9-33798840-T-C

Variant names:

• chr9-33798840-T-C
• rs41315997
• NM_002771.4:c.592-188T>C

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.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
• Publications: 0 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=-0.89).
• BP6: Variant 9-33798840-T-C is Benign according to our data. Variant chr9-33798840-T-C is described in ClinVar as Benign. ClinVar VariationId 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.

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.592-188T>C		intron	N/A	NP_002762.3
	PRSS3	NM_001197097.3		c.634-188T>C		intron	N/A	NP_001184026.3	P35030-4
	PRSS3	NM_001197098.1		c.571-188T>C		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.592-188T>C		intron	N/A	ENSP00000368715.3	P35030-3
	PRSS3	ENST00000342836.9	TSL:1	c.628-188T>C		intron	N/A	ENSP00000340889.5	A0A7P0MNE9
	PRSS3	ENST00000429677.8	TSL:1	c.571-188T>C		intron	N/A	ENSP00000401828.3	P35030-5

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

African (AFR) AF: 0.0132 AC: 278 AN: 21056

American (AMR) AF: 0.0341 AC: 891 AN: 26152

Ashkenazi Jewish (ASJ) AF: 0.0403 AC: 703 AN: 17426

East Asian (EAS) AF: 0.00327 AC: 112 AN: 34226

South Asian (SAS) AF: 0.0454 AC: 2712 AN: 59772

European-Finnish (FIN) AF: 0.108 AC: 4910 AN: 45332

Middle Eastern (MID) AF: 0.0494 AC: 146 AN: 2954

European-Non Finnish (NFE) AF: 0.0867 AC: 55413 AN: 639302

Other (OTH) AF: 0.0659 AC: 2669 AN: 40522

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

African (AFR) AF: 0.0143 AC: 594 AN: 41472

American (AMR) AF: 0.0413 AC: 632 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.0409 AC: 142 AN: 3468

East Asian (EAS) AF: 0.00483 AC: 25 AN: 5174

South Asian (SAS) AF: 0.0440 AC: 212 AN: 4814

European-Finnish (FIN) AF: 0.116 AC: 1229 AN: 10568

Middle Eastern (MID) AF: 0.0374 AC: 11 AN: 294

European-Non Finnish (NFE) AF: 0.0910 AC: 6182 AN: 67928

Other (OTH) AF: 0.0546 AC: 115 AN: 2106

Alfa AF: 0.0625 Hom.: 172

Bravo AF: 0.0511

Asia WGS AF: 0.0220 AC: 76 AN: 3478

ClinVar

ClinVar submissions

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	-0.89
CADD	Benign	4.8
DANN	Benign	0.23
PhyloP100		1.0
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: rs41315997; hg19: chr9-33798838;