rs855581

Variant names:

• chr9-33798019-A-G
• rs855581
• NM_002771.4:c.391A>G

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Strong BP6_Moderate

The NM_002771.4(PRSS3):​c.391A>G​(p.Thr131Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.70 (27687 hom., cov: 38)
  • Exomes 𝑓: 0.73 (316286 hom.)
  • Failed GnomAD Quality Control
• Consequence: PRSS3 NM_002771.4 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.108
• Publications: 24 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: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=1.1308639E-6).
• BP6: Variant 9-33798019-A-G is Benign according to our data. Variant chr9-33798019-A-G is described in ClinVar as Benign. ClinVar VariationId is 2786908.Status of the report is criteria_provided_single_submitter, 1 stars.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRSS3	NM_002771.4	MANE Select	c.391A>G	p.Thr131Ala	missense	Exon 3 of 5	NP_002762.3
	PRSS3	NM_001197097.3		c.433A>G	p.Thr145Ala	missense	Exon 4 of 6	NP_001184026.3
	PRSS3	NM_001197098.1		c.370A>G	p.Thr124Ala	missense	Exon 3 of 5	NP_001184027.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRSS3	ENST00000379405.4	TSL:1 MANE Select	c.391A>G	p.Thr131Ala	missense	Exon 3 of 5	ENSP00000368715.3
	PRSS3	ENST00000342836.9	TSL:1	c.427A>G	p.Thr143Ala	missense	Exon 4 of 6	ENSP00000340889.5
	PRSS3	ENST00000429677.8	TSL:1	c.370A>G	p.Thr124Ala	missense	Exon 3 of 5	ENSP00000401828.3

Frequencies

GnomAD3 genomes AF: 0.704 AC: 95619 AN: 135884 Hom.: 27684 Cov.: 38

Gnomad AFR AF: 0.633

Gnomad AMI AF: 0.730

Gnomad AMR AF: 0.712

Gnomad ASJ AF: 0.718

Gnomad EAS AF: 0.890

Gnomad SAS AF: 0.835

Gnomad FIN AF: 0.710

Gnomad MID AF: 0.771

Gnomad NFE AF: 0.718

Gnomad OTH AF: 0.704

GnomAD2 exomes AF: 0.960 AC: 233319 AN: 243014 AF XY: 0.962

Gnomad AFR exome AF: 0.902

Gnomad AMR exome AF: 0.955

Gnomad ASJ exome AF: 0.962

Gnomad EAS exome AF: 0.990

Gnomad FIN exome AF: 0.960

Gnomad NFE exome AF: 0.958

Gnomad OTH exome AF: 0.964

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR;InbreedingCoeff AF: 0.726 AC: 1015042 AN: 1397528 Hom.: 316286 Cov.: 100 AF XY: 0.730 AC XY: 508137 AN XY: 696372

African (AFR) AF: 0.644 AC: 20650 AN: 32056

American (AMR) AF: 0.739 AC: 31770 AN: 42976

Ashkenazi Jewish (ASJ) AF: 0.750 AC: 18696 AN: 24920

East Asian (EAS) AF: 0.919 AC: 35171 AN: 38254

South Asian (SAS) AF: 0.849 AC: 71282 AN: 83932

European-Finnish (FIN) AF: 0.756 AC: 38467 AN: 50866

Middle Eastern (MID) AF: 0.749 AC: 4164 AN: 5558

European-Non Finnish (NFE) AF: 0.708 AC: 751413 AN: 1061294

Other (OTH) AF: 0.753 AC: 43429 AN: 57672

GnomAD4 genome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.704 AC: 95682 AN: 136004 Hom.: 27687 Cov.: 38 AF XY: 0.703 AC XY: 46813 AN XY: 66578

African (AFR) AF: 0.633 AC: 23365 AN: 36930

American (AMR) AF: 0.712 AC: 9576 AN: 13454

Ashkenazi Jewish (ASJ) AF: 0.718 AC: 2233 AN: 3110

East Asian (EAS) AF: 0.890 AC: 4272 AN: 4800

South Asian (SAS) AF: 0.835 AC: 3597 AN: 4310

European-Finnish (FIN) AF: 0.710 AC: 6689 AN: 9418

Middle Eastern (MID) AF: 0.765 AC: 202 AN: 264

European-Non Finnish (NFE) AF: 0.718 AC: 43825 AN: 61026

Other (OTH) AF: 0.708 AC: 1329 AN: 1878

Alfa AF: 0.838 Hom.: 12958

ExAC AF: 0.910 AC: 110526

Asia WGS AF: 0.999 AC: 3475 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.070
BayesDel_addAF	Benign	-0.019	T
BayesDel_noAF	Benign	-0.27
CADD	Benign	0.66
DANN	Benign	0.58
DEOGEN2	Benign	0.16	T
Eigen	Benign	-1.7
Eigen_PC	Benign	-1.7
FATHMM_MKL	Benign	0.0094	N
LIST_S2	Benign	0.0091	T
MetaRNN	Benign	0.0000011	T
MetaSVM	Benign	-0.86	T
MutationAssessor	Benign	0.47	N
PhyloP100		-0.11
PrimateAI	Uncertain	0.55	T
PROVEAN	Benign	0.91	N
REVEL	Uncertain	0.39
Sift	Benign	0.43	T
Sift4G	Benign	0.44	T
Polyphen		0.0	B
Vest4		0.070
MPC		0.24
ClinPred		0.00030	T
GERP RS		-4.3
Varity_R		0.026
gMVP		0.17
Mutation Taster		=96/4	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: rs855581; hg19: chr9-33798017; COSMIC: COSV61553087; COSMIC: COSV61553087;