9-33797763-G-C

Variant names:

• chr9-33797763-G-C
• rs83922
• NM_002771.4:c.201-66G>C

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_002771.4(PRSS3):​c.201-66G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00155 in 1,503,030 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.017 (0 hom., cov: 36)
  • Exomes 𝑓: 0.00011 (0 hom.)
• Consequence: PRSS3 NM_002771.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0740
• Publications: 4 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 -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).

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.201-66G>C		intron	N/A	NP_002762.3
	PRSS3	NM_001197097.3		c.243-66G>C		intron	N/A	NP_001184026.3	P35030-4
	PRSS3	NM_001197098.1		c.180-66G>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.201-66G>C		intron	N/A	ENSP00000368715.3	P35030-3
	PRSS3	ENST00000342836.9	TSL:1	c.237-66G>C		intron	N/A	ENSP00000340889.5	A0A7P0MNE9
	PRSS3	ENST00000429677.8	TSL:1	c.180-66G>C		intron	N/A	ENSP00000401828.3	P35030-5

Frequencies

GnomAD3 genomes AF: 0.0169 AC: 2178 AN: 128578 Hom.: 0 Cov.: 36

Gnomad AFR AF: 0.0188

Gnomad AMI AF: 0.00648

Gnomad AMR AF: 0.0207

Gnomad ASJ AF: 0.0127

Gnomad EAS AF: 0.00685

Gnomad SAS AF: 0.00859

Gnomad FIN AF: 0.0206

Gnomad MID AF: 0.00730

Gnomad NFE AF: 0.0161

Gnomad OTH AF: 0.0195

GnomAD4 exome AF: 0.000110 AC: 151 AN: 1374348 Hom.: 0 AF XY: 0.000133 AC XY: 91 AN XY: 682800

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.0000322 AC: 1 AN: 31086

American (AMR) AF: 0.000196 AC: 8 AN: 40840

Ashkenazi Jewish (ASJ) AF: 0.000212 AC: 5 AN: 23580

East Asian (EAS) AF: 0.0000269 AC: 1 AN: 37212

South Asian (SAS) AF: 0.0000126 AC: 1 AN: 79170

European-Finnish (FIN) AF: 0.000582 AC: 27 AN: 46378

Middle Eastern (MID) AF: 0.000750 AC: 4 AN: 5336

European-Non Finnish (NFE) AF: 0.0000853 AC: 90 AN: 1054634

Other (OTH) AF: 0.000250 AC: 14 AN: 56112

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.0169 AC: 2180 AN: 128682 Hom.: 0 Cov.: 36 AF XY: 0.0182 AC XY: 1146 AN XY: 62968

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.0188 AC: 662 AN: 35304

American (AMR) AF: 0.0207 AC: 267 AN: 12892

Ashkenazi Jewish (ASJ) AF: 0.0127 AC: 36 AN: 2828

East Asian (EAS) AF: 0.00686 AC: 32 AN: 4662

South Asian (SAS) AF: 0.00860 AC: 37 AN: 4300

European-Finnish (FIN) AF: 0.0206 AC: 192 AN: 9298

Middle Eastern (MID) AF: 0.00794 AC: 2 AN: 252

European-Non Finnish (NFE) AF: 0.0161 AC: 913 AN: 56602

Other (OTH) AF: 0.0192 AC: 34 AN: 1772

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00 Hom.: 401

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	6.1
DANN	Benign	0.81
PhyloP100		-0.074

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.090		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: rs83922; hg19: chr9-33797761;