9-33796914-A-G

Variant names:

• chr9-33796914-A-G
• rs855580
• NM_002771.4:c.200+112A>G

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.200+112A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.96 in 151,580 control chromosomes in the GnomAD database, including 69,883 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.96 (69883 hom., cov: 31)
  • Exomes 𝑓: 0.99 (686750 hom.)
  • Failed GnomAD Quality Control
• Consequence: PRSS3 NM_002771.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.925
• Publications: 1 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=-0.96).
• BP6: Variant 9-33796914-A-G is Benign according to our data. Variant chr9-33796914-A-G is described in ClinVar as Benign. ClinVar VariationId is 1291262.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.99 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.200+112A>G		intron	N/A	NP_002762.3
	PRSS3	NM_001197097.3		c.242+112A>G		intron	N/A	NP_001184026.3	P35030-4
	PRSS3	NM_001197098.1		c.179+112A>G		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.200+112A>G		intron	N/A	ENSP00000368715.3	P35030-3
	PRSS3	ENST00000342836.9	TSL:1	c.236+112A>G		intron	N/A	ENSP00000340889.5	A0A7P0MNE9
	PRSS3	ENST00000429677.8	TSL:1	c.179+112A>G		intron	N/A	ENSP00000401828.3	P35030-5

Frequencies

GnomAD3 genomes AF: 0.960 AC: 145409 AN: 151470 Hom.: 69838 Cov.: 31

Gnomad AFR AF: 0.901

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.960

Gnomad ASJ AF: 0.992

Gnomad EAS AF: 0.911

Gnomad SAS AF: 0.972

Gnomad FIN AF: 0.958

Gnomad MID AF: 0.990

Gnomad NFE AF: 0.996

Gnomad OTH AF: 0.975

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.987 AC: 1391056 AN: 1409588 Hom.: 686750 AF XY: 0.987 AC XY: 693518 AN XY: 702798

African (AFR) AF: 0.897 AC: 28802 AN: 32124

American (AMR) AF: 0.958 AC: 39856 AN: 41616

Ashkenazi Jewish (ASJ) AF: 0.989 AC: 25387 AN: 25668

East Asian (EAS) AF: 0.867 AC: 33627 AN: 38776

South Asian (SAS) AF: 0.978 AC: 82359 AN: 84248

European-Finnish (FIN) AF: 0.959 AC: 50387 AN: 52560

Middle Eastern (MID) AF: 0.982 AC: 5500 AN: 5602

European-Non Finnish (NFE) AF: 0.997 AC: 1067558 AN: 1070320

Other (OTH) AF: 0.981 AC: 57580 AN: 58674

GnomAD4 genome AF: 0.960 AC: 145509 AN: 151580 Hom.: 69883 Cov.: 31 AF XY: 0.958 AC XY: 70975 AN XY: 74090

African (AFR) AF: 0.901 AC: 37111 AN: 41200

American (AMR) AF: 0.960 AC: 14640 AN: 15248

Ashkenazi Jewish (ASJ) AF: 0.992 AC: 3438 AN: 3466

East Asian (EAS) AF: 0.910 AC: 4683 AN: 5144

South Asian (SAS) AF: 0.972 AC: 4667 AN: 4800

European-Finnish (FIN) AF: 0.958 AC: 10098 AN: 10544

Middle Eastern (MID) AF: 0.990 AC: 289 AN: 292

European-Non Finnish (NFE) AF: 0.996 AC: 67610 AN: 67860

Other (OTH) AF: 0.975 AC: 2061 AN: 2114

Alfa AF: 0.926 Hom.: 7119

Bravo AF: 0.958

Asia WGS AF: 0.922 AC: 3206 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	-0.96
CADD	Benign	0.55
DANN	Benign	0.69
PhyloP100		-0.93
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: rs855580; hg19: chr9-33796912; COSMIC: COSV61560685; COSMIC: COSV61560685;