7-142751933-C-T

Variant names:

• chr7-142751933-C-T
• rs606231348
• NM_002769.5:c.360C>T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP6_Very_Strong BP7

The NM_002769.5(PRSS1):​c.360C>T​(p.Asn120Asn) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.00020 (0 hom., cov: 31)
  • Exomes 𝑓: 0.000032 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: PRSS1 NM_002769.5 synonymous
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts U:1 B:4
• Conservation: PhyloP100: 0.242

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]

TRB (HGNC:12155):

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 7-142751933-C-T is Benign according to our data. Variant chr7-142751933-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 161989.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.242 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRSS1	NM_002769.5	c.360C>T	p.Asn120Asn	synonymous_variant	Exon 3 of 5	ENST00000311737.12	NP_002760.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRSS1	ENST00000311737.12	c.360C>T	p.Asn120Asn	synonymous_variant	Exon 3 of 5	1	NM_002769.5	ENSP00000308720.7

Frequencies

GnomAD3 genomes AF: 0.00 AC: 29 AN: 143290 Hom.: 0 Cov.: 31 FAILED QC

Gnomad AFR AF: 0.000534

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000140

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000431

Gnomad FIN AF: 0.000101

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000611

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.0000241 AC: 6 AN: 249414 Hom.: 0 AF XY: 0.00000740 AC XY: 1 AN XY: 135160

Gnomad AFR exome AF: 0.000186

Gnomad AMR exome AF: 0.0000290

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000327

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000886

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000324 AC: 46 AN: 1420922 Hom.: 0 Cov.: 62 AF XY: 0.0000339 AC XY: 24 AN XY: 708528

Gnomad4 AFR exome AF: 0.000157

Gnomad4 AMR exome AF: 0.0000703

Gnomad4 ASJ exome AF: 0.0000393

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000586

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000241

Gnomad4 OTH exome AF: 0.0000846

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.000202 AC: 29 AN: 143390 Hom.: 0 Cov.: 31 AF XY: 0.000157 AC XY: 11 AN XY: 70068

Gnomad4 AFR AF: 0.000533

Gnomad4 AMR AF: 0.000139

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000431

Gnomad4 FIN AF: 0.000101

Gnomad4 NFE AF: 0.0000611

Gnomad4 OTH AF: 0.00

Alfa AF: 0.0000354 Hom.: 0

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Uncertain:1 Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Hereditary pancreatitis Uncertain:1 Benign:2

Feb 12, 2021

Ambry Genetics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Sep 08, 2023

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

Forschungslabor Klinik Innere Medizin A University Medicine Greifswald

Significance: Uncertain significance

Review Status: no assertion criteria provided

Collection Method: literature only

- -

not specified Benign:1

Jul 24, 2019

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided Benign:1

May 11, 2017

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The PRSS1 c.360C>T, p.Asn120Asn variant (rs606231348) has not been reported in the medical literature, but is listed in ClinVar (Variation ID: 161989). It is observed in the Genome Aggregation Database at a frequency of 0.004 percent (11/274710), but is considered a low-confidence variant. The variant is a synonymous substitution, and computational algorithms (GeneSplicer, Human Splicing Finder, MaxEntScan, MutationTaster, NNSplice, SpliceSiteFinder-like) predict no impact on splicing. Based on the above information, the variant is considered likely benign. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	5.8
DANN	Benign	0.54

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs606231348; hg19: chr7-142459784;