rs855581

chr9-33798019-A-G

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

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. 13/20 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

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 -10 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 id is 2786908.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAdExome at 111817 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PRSS3	NM_002771.4	c.391A>G	p.Thr131Ala	missense_variant	3/5	ENST00000379405.4
UBE2R2-AS1	NR_170204.1	n.558+349T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PRSS3	ENST00000379405.4	c.391A>G	p.Thr131Ala	missense_variant	3/5	1	NM_002771.4	P1
UBE2R2-AS1	ENST00000705030.1	n.425+349T>C		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.00 AC: 95619 AN: 135884 Hom.: 27684 Cov.: 38 FAILED QC

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

GnomAD3 exomes AF: 0.960 AC: 233319 AN: 243014 Hom.: 111817 AF XY: 0.962 AC XY: 126489 AN XY: 131442

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 SAS exome AF: 0.986

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

Gnomad4 AFR exome AF: 0.644

Gnomad4 AMR exome AF: 0.739

Gnomad4 ASJ exome AF: 0.750

Gnomad4 EAS exome AF: 0.919

Gnomad4 SAS exome AF: 0.849

Gnomad4 FIN exome AF: 0.756

Gnomad4 NFE exome AF: 0.708

Gnomad4 OTH exome AF: 0.753

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

Gnomad4 AFR AF: 0.633

Gnomad4 AMR AF: 0.712

Gnomad4 ASJ AF: 0.718

Gnomad4 EAS AF: 0.890

Gnomad4 SAS AF: 0.835

Gnomad4 FIN AF: 0.710

Gnomad4 NFE AF: 0.718

Gnomad4 OTH AF: 0.708

Alfa AF: 0.756 Hom.: 6490

ExAC AF: 0.910 AC: 110526

Asia WGS AF: 0.999 AC: 3475 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

Invitae

Jan 17, 2024

- -

Computational scores

Source: dbNSFP v4.3

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
Eigen	Benign	-1.7
Eigen_PC	Benign	-1.7
FATHMM_MKL	Benign	0.0094	N
LIST_S2	Benign	0.0091	T;T;T;T;T
MetaRNN	Benign	0.0000011	T;T;T;T;T
MetaSVM	Benign	-0.86	T
MutationTaster	Benign	1.0	P;P;P;P
PrimateAI	Uncertain	0.55	T
PROVEAN	Benign	0.91	N;N;N;N;N
REVEL	Uncertain	0.39
Sift	Benign	0.43	T;T;T;T;T
Sift4G	Benign	0.44	T;T;T;T;T
Polyphen		0.0	B;B;.;.;B
Vest4		0.070
MPC		0.24
ClinPred		0.00030	T
GERP RS		-4.3
Varity_R		0.026
gMVP		0.17

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: rs855581; hg19: chr9-33798017; COSMIC: COSV61553087; COSMIC: COSV61553087;