9-33794842-G-A

Variant names:

• chr9-33794842-G-A
• rs10117993
• ENST00000342836.9:c.45G>A

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_001197097.3(PRSS3):​c.51G>A​(p.Ala17Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0145 in 1,402,726 control chromosomes in the GnomAD database, including 1,619 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.10 (854 hom., cov: 33)
  • Exomes 𝑓: 0.0069 (765 hom.)
• Consequence: PRSS3 NM_001197097.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.323

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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 9-33794842-G-A is Benign according to our data. Variant chr9-33794842-G-A is described in ClinVar as [Benign]. Clinvar id is 1271011.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.323 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.283 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRSS3	NM_001197097.3	c.51G>A	p.Ala17Ala	synonymous_variant	Exon 2 of 6		NP_001184026.3
PRSS3	XM_047423602.1	c.-732G>A		5_prime_UTR_variant	Exon 2 of 6		XP_047279558.1
PRSS3	NM_001197098.1	c.20-1801G>A		intron_variant	Intron 1 of 4		NP_001184027.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRSS3	ENST00000342836.9	c.45G>A	p.Ala15Ala	synonymous_variant	Exon 2 of 6	1		ENSP00000340889.5
PRSS3	ENST00000429677.8	c.20-1801G>A		intron_variant	Intron 1 of 4	1		ENSP00000401828.3
PRSS3	ENST00000361005.10	c.-284-1801G>A		intron_variant	Intron 1 of 4	1		ENSP00000354280.6

Frequencies

GnomAD3 genomes AF: 0.104 AC: 11360 AN: 109732 Hom.: 846 Cov.: 33

Gnomad AFR AF: 0.287

Gnomad AMI AF: 0.0205

Gnomad AMR AF: 0.0610

Gnomad ASJ AF: 0.0241

Gnomad EAS AF: 0.00579

Gnomad SAS AF: 0.0119

Gnomad FIN AF: 0.0398

Gnomad MID AF: 0.0294

Gnomad NFE AF: 0.0254

Gnomad OTH AF: 0.0805

GnomAD2 exomes AF: 0.0125 AC: 1856 AN: 148268 AF XY: 0.00955

Gnomad AFR exome AF: 0.207

Gnomad AMR exome AF: 0.0125

Gnomad ASJ exome AF: 0.000120

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000243

Gnomad NFE exome AF: 0.00157

Gnomad OTH exome AF: 0.00927

GnomAD4 exome AF: 0.00691 AC: 8928 AN: 1292910 Hom.: 765 Cov.: 32 AF XY: 0.00602 AC XY: 3845 AN XY: 638184

Gnomad4 AFR exome AF: 0.224 AC: 6612 AN: 29542

Gnomad4 AMR exome AF: 0.0155 AC: 514 AN: 33102

Gnomad4 ASJ exome AF: 0.000308 AC: 7 AN: 22744

Gnomad4 EAS exome AF: 0.000117 AC: 4 AN: 34290

Gnomad4 SAS exome AF: 0.00104 AC: 79 AN: 75820

Gnomad4 FIN exome AF: 0.000925 AC: 39 AN: 42180

Gnomad4 NFE exome AF: 0.000658 AC: 656 AN: 996658

Gnomad4 Remaining exome AF: 0.0176 AC: 939 AN: 53322

GnomAD4 genome AF: 0.104 AC: 11408 AN: 109816 Hom.: 854 Cov.: 33 AF XY: 0.102 AC XY: 5479 AN XY: 53722

Gnomad4 AFR AF: 0.288 AC: 0.288199 AN: 0.288199

Gnomad4 AMR AF: 0.0609 AC: 0.0608891 AN: 0.0608891

Gnomad4 ASJ AF: 0.0241 AC: 0.0241064 AN: 0.0241064

Gnomad4 EAS AF: 0.00580 AC: 0.00580357 AN: 0.00580357

Gnomad4 SAS AF: 0.0119 AC: 0.0119471 AN: 0.0119471

Gnomad4 FIN AF: 0.0398 AC: 0.0397727 AN: 0.0397727

Gnomad4 NFE AF: 0.0254 AC: 0.0253655 AN: 0.0253655

Gnomad4 OTH AF: 0.0786 AC: 0.078629 AN: 0.078629

Alfa AF: 0.0918 Hom.: 169

Asia WGS AF: 0.0140 AC: 50 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Aug 15, 2019

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	1.2
DANN	Benign	0.75
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs10117993; hg19: chr9-33794840; COSMIC: COSV61554235; COSMIC: COSV61554235;