7-142752026-C-G

Variant names:

• chr7-142752026-C-G
• rs147765409
• NM_002769.5:c.453C>G

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4_Strong BP7

The NM_002769.5(PRSS1):​c.453C>G​(p.Gly151Gly) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. G151G) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.00046 (0 hom., cov: 30)
  • Exomes 𝑓: 0.000038 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: PRSS1 NM_002769.5 splice_region, synonymous
• Scores: Splicing: ADA: 0.0006134
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.21
• Publications: 3 publications found

Genes affected

PRSS1 (HGNC:9475): (serine protease 1) This gene encodes a trypsinogen, which is a member of the trypsin family of serine proteases. This enzyme is secreted by the pancreas and cleaved to its active form in the small intestine. It is active on peptide linkages involving the carboxyl group of lysine or arginine. Mutations in this gene are associated with hereditary pancreatitis. This gene and several other trypsinogen genes are localized to the T cell receptor beta locus on chromosome 7. [provided by RefSeq, Jul 2008]

PRSS1 Gene-Disease associations (from GenCC):

• hereditary chronic pancreatitis

  Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, ClinGen, PanelApp Australia, Illumina, Labcorp Genetics (formerly Invitae), Ambry Genetics
• malignant pancreatic neoplasm

  Inheritance: AD Classification: MODERATE Submitted by: Genomics England PanelApp

TRB (HGNC:12155):

ACMG classification

Our verdict: Likely_benign. The variant received -5 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.64).
• BP7: Synonymous conserved (PhyloP=-2.21 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002769.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRSS1	NM_002769.5	MANE Select	c.453C>G	p.Gly151Gly	splice_region synonymous	Exon 3 of 5	NP_002760.1
	PRSS1	NR_172947.1		n.395C>G		splice_region non_coding_transcript_exon	Exon 3 of 5
	PRSS1	NR_172948.1		n.392C>G		splice_region non_coding_transcript_exon	Exon 3 of 5

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRSS1	ENST00000311737.12	TSL:1 MANE Select	c.453C>G	p.Gly151Gly	splice_region synonymous	Exon 3 of 5	ENSP00000308720.7
	PRSS1	ENST00000486171.5	TSL:5	c.495C>G	p.Gly165Gly	splice_region synonymous	Exon 4 of 6	ENSP00000417854.1
	PRSS1	ENST00000492062.2	TSL:2	c.453C>G	p.Gly151Gly	splice_region synonymous	Exon 3 of 5	ENSP00000419912.2

Frequencies

GnomAD3 genomes AF: 0.000460 AC: 58 AN: 125976 Hom.: 0 Cov.: 30

Gnomad AFR AF: 0.000494

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000319

Gnomad ASJ AF: 0.000339

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000118

Gnomad MID AF: 0.00352

Gnomad NFE AF: 0.000571

Gnomad OTH AF: 0.00118

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000382 AC: 50 AN: 1309612 Hom.: 0 Cov.: 60 AF XY: 0.0000397 AC XY: 26 AN XY: 655004

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

African (AFR) AF: 0.000107 AC: 3 AN: 27988

American (AMR) AF: 0.0000514 AC: 2 AN: 38874

Ashkenazi Jewish (ASJ) AF: 0.0000857 AC: 2 AN: 23328

East Asian (EAS) AF: 0.00 AC: 0 AN: 39474

South Asian (SAS) AF: 0.0000121 AC: 1 AN: 82376

European-Finnish (FIN) AF: 0.000605 AC: 29 AN: 47958

Middle Eastern (MID) AF: 0.00123 AC: 6 AN: 4876

European-Non Finnish (NFE) AF: 0.00000607 AC: 6 AN: 989046

Other (OTH) AF: 0.0000180 AC: 1 AN: 55692

⚠️ 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 Data not reliable, filtered out with message: AS_VQSR AF: 0.000460 AC: 58 AN: 126030 Hom.: 0 Cov.: 30 AF XY: 0.000554 AC XY: 34 AN XY: 61348

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

African (AFR) AF: 0.000493 AC: 16 AN: 32464

American (AMR) AF: 0.000319 AC: 4 AN: 12540

Ashkenazi Jewish (ASJ) AF: 0.000339 AC: 1 AN: 2954

East Asian (EAS) AF: 0.00 AC: 0 AN: 4772

South Asian (SAS) AF: 0.00 AC: 0 AN: 4252

European-Finnish (FIN) AF: 0.000118 AC: 1 AN: 8496

Middle Eastern (MID) AF: 0.00385 AC: 1 AN: 260

European-Non Finnish (NFE) AF: 0.000571 AC: 33 AN: 57806

Other (OTH) AF: 0.00117 AC: 2 AN: 1708

⚠️ 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.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.64
CADD	Benign	0.020
DANN	Benign	0.30
PhyloP100		-2.2

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00061
dbscSNV1_RF	Benign	0.24
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: rs147765409; hg19: chr7-142459877;