chr9-33796692-TGAG-T

Variant names:

• chr9-33796692-TGAG-T
• rs3831310
• NM_002771.4:c.94_96delGAG

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 1P and 10B. PM4_Supporting BP6_Moderate BA1

The NM_002771.4(PRSS3):​c.94_96delGAG​(p.Glu32del) variant causes a conservative inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.168 in 1,610,864 control chromosomes in the GnomAD database, including 4,652 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.14 (1087 hom., cov: 32)
  • Exomes 𝑓: 0.17 (3565 hom.)
• Consequence: PRSS3 NM_002771.4 conservative_inframe_deletion
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.192

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 -9 ACMG points.

• PM4: Nonframeshift variant in NON repetitive region in NM_002771.4. Strenght limited to Supporting due to length of the change: 1aa.
• BP6: Variant 9-33796692-TGAG-T is Benign according to our data. Variant chr9-33796692-TGAG-T is described in ClinVar as [Benign]. Clinvar id is 1225003.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.295 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRSS3	NM_002771.4	c.94_96delGAG	p.Glu32del	conservative_inframe_deletion	Exon 2 of 5	ENST00000379405.4	NP_002762.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRSS3	ENST00000379405.4	c.94_96delGAG	p.Glu32del	conservative_inframe_deletion	Exon 2 of 5	1	NM_002771.4	ENSP00000368715.3

Frequencies

GnomAD3 genomes AF: 0.145 AC: 21935 AN: 151580 Hom.: 1082 Cov.: 32

Gnomad AFR AF: 0.0639

Gnomad AMI AF: 0.104

Gnomad AMR AF: 0.156

Gnomad ASJ AF: 0.138

Gnomad EAS AF: 0.0854

Gnomad SAS AF: 0.309

Gnomad FIN AF: 0.192

Gnomad MID AF: 0.118

Gnomad NFE AF: 0.178

Gnomad OTH AF: 0.150

GnomAD2 exomes AF: 0.171 AC: 42943 AN: 250786 AF XY: 0.178

Gnomad AFR exome AF: 0.0642

Gnomad AMR exome AF: 0.166

Gnomad ASJ exome AF: 0.136

Gnomad EAS exome AF: 0.0801

Gnomad FIN exome AF: 0.201

Gnomad NFE exome AF: 0.170

Gnomad OTH exome AF: 0.169

GnomAD4 exome AF: 0.170 AC: 248064 AN: 1459164 Hom.: 3565 AF XY: 0.174 AC XY: 125966 AN XY: 725796

Gnomad4 AFR exome AF: 0.0591 AC: 1976 AN: 33452

Gnomad4 AMR exome AF: 0.162 AC: 7223 AN: 44622

Gnomad4 ASJ exome AF: 0.133 AC: 3478 AN: 26084

Gnomad4 EAS exome AF: 0.0823 AC: 3266 AN: 39686

Gnomad4 SAS exome AF: 0.281 AC: 24132 AN: 85916

Gnomad4 FIN exome AF: 0.202 AC: 10768 AN: 53298

Gnomad4 NFE exome AF: 0.168 AC: 186363 AN: 1110090

Gnomad4 Remaining exome AF: 0.168 AC: 10121 AN: 60264

GnomAD4 genome AF: 0.145 AC: 21947 AN: 151700 Hom.: 1087 Cov.: 32 AF XY: 0.147 AC XY: 10916 AN XY: 74152

Gnomad4 AFR AF: 0.0637 AC: 0.0637165 AN: 0.0637165

Gnomad4 AMR AF: 0.157 AC: 0.157373 AN: 0.157373

Gnomad4 ASJ AF: 0.138 AC: 0.137832 AN: 0.137832

Gnomad4 EAS AF: 0.0856 AC: 0.0855594 AN: 0.0855594

Gnomad4 SAS AF: 0.308 AC: 0.308239 AN: 0.308239

Gnomad4 FIN AF: 0.192 AC: 0.191622 AN: 0.191622

Gnomad4 NFE AF: 0.178 AC: 0.177941 AN: 0.177941

Gnomad4 OTH AF: 0.151 AC: 0.151096 AN: 0.151096

Alfa AF: 0.170 Hom.: 221

Asia WGS AF: 0.172 AC: 600 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Aug 15, 2019

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
Mutation Taster		=77/23	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.11		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: rs3831310; hg19: chr9-33796690; COSMIC: COSV61552946; COSMIC: COSV61552946;