9-33797763-G-T

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_002771.4(PRSS3):​c.201-66G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0027 in 1,486,938 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.027 (0 hom., cov: 36)
  • Exomes 𝑓: 0.00058 (0 hom.)
• Consequence: PRSS3 NM_002771.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• 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.

• PM2: Variant has high frequency in the MID (0.00161) population. However there is too low homozygotes in high coverage region: (expected more than 2, got 0).
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 9-33797763-G-T is Benign according to our data. Variant chr9-33797763-G-T is described in ClinVar as Benign. ClinVar VariationId is 1245449.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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRSS3	NM_002771.4	MANE Select	c.201-66G>T		intron	N/A	NP_002762.3
	PRSS3	NM_001197097.3		c.243-66G>T		intron	N/A	NP_001184026.3	P35030-4
	PRSS3	NM_001197098.1		c.180-66G>T		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>T		intron	N/A	ENSP00000368715.3	P35030-3
	PRSS3	ENST00000342836.9	TSL:1	c.237-66G>T		intron	N/A	ENSP00000340889.5	A0A7P0MNE9
	PRSS3	ENST00000429677.8	TSL:1	c.180-66G>T		intron	N/A	ENSP00000401828.3	P35030-5

Frequencies

GnomAD3 genomes AF: 0.0266 AC: 3201 AN: 120194 Hom.: 0 Cov.: 36

Gnomad AFR AF: 0.0422

Gnomad AMI AF: 0.0180

Gnomad AMR AF: 0.0258

Gnomad ASJ AF: 0.0163

Gnomad EAS AF: 0.00709

Gnomad SAS AF: 0.0109

Gnomad FIN AF: 0.0418

Gnomad MID AF: 0.0254

Gnomad NFE AF: 0.0190

Gnomad OTH AF: 0.0286

GnomAD4 exome AF: 0.000584 AC: 798 AN: 1366670 Hom.: 0 AF XY: 0.000620 AC XY: 421 AN XY: 679274

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

African (AFR) AF: 0.00197 AC: 58 AN: 29438

American (AMR) AF: 0.000758 AC: 31 AN: 40894

Ashkenazi Jewish (ASJ) AF: 0.00139 AC: 32 AN: 23068

East Asian (EAS) AF: 0.000381 AC: 14 AN: 36728

South Asian (SAS) AF: 0.0000121 AC: 1 AN: 82348

European-Finnish (FIN) AF: 0.00191 AC: 88 AN: 46136

Middle Eastern (MID) AF: 0.00266 AC: 14 AN: 5264

European-Non Finnish (NFE) AF: 0.000474 AC: 497 AN: 1047418

Other (OTH) AF: 0.00114 AC: 63 AN: 55376

⚠️ 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: 0.0267 AC: 3213 AN: 120268 Hom.: 0 Cov.: 36 AF XY: 0.0291 AC XY: 1709 AN XY: 58772

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

African (AFR) AF: 0.0425 AC: 1331 AN: 31342

American (AMR) AF: 0.0258 AC: 311 AN: 12044

Ashkenazi Jewish (ASJ) AF: 0.0163 AC: 44 AN: 2696

East Asian (EAS) AF: 0.00733 AC: 33 AN: 4504

South Asian (SAS) AF: 0.0109 AC: 45 AN: 4114

European-Finnish (FIN) AF: 0.0418 AC: 347 AN: 8298

Middle Eastern (MID) AF: 0.0275 AC: 6 AN: 218

European-Non Finnish (NFE) AF: 0.0190 AC: 1038 AN: 54698

Other (OTH) AF: 0.0276 AC: 45 AN: 1630

⚠️ 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: 0.283 Hom.: 401

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
BayesDel_noAF	Benign	-0.83
CADD	Benign	2.1
DANN	Benign	0.86
PhyloP100		-0.074
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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;