NM_002769.5(PRSS1):c.453C>T (p.Gly151=) AND Hereditary pancreatitis

Germline classification:: Conflicting interpretations of pathogenicity (2 submissions)
Last evaluated:: May 5, 2023
Review status:: criteria provided, conflicting classifications

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV000468352.16

Allele description [Variation Report for NM_002769.5(PRSS1):c.453C>T (p.Gly151=)]

NM_002769.5(PRSS1):c.453C>T (p.Gly151=)

Genes:

TRB:T cell receptor beta locus [Gene - HGNC]
PRSS1:serine protease 1 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

7q34

Genomic location:

Preferred name:

NM_002769.5(PRSS1):c.453C>T (p.Gly151=)

HGVS:

NC_000007.14:g.142752026C>T
NG_001333.2:g.585694C>T
NG_008307.3:g.7543C>T
NM_002769.5:c.453C>TMANE SELECT
NP_002760.1:p.Gly151=
LRG_1013t1:c.453C>T
LRG_1013:g.7543C>T
LRG_1013p1:p.Gly151=
NC_000007.13:g.142459877C>T
NM_002769.4:c.453C>T
p.Gly151Gly

Links:

dbSNP: rs147765409

NCBI 1000 Genomes Browser:

rs147765409

Molecular consequence:

NM_002769.5:c.453C>T - synonymous variant - [Sequence Ontology: SO:0001819]

Observations:

Condition(s)

Name:: Hereditary pancreatitis (PCTT)
Synonyms:: Hereditary chronic pancreatitis
Identifiers:: MONDO: MONDO:0008185; MedGen: C0238339; Orphanet: 676; OMIM: 167800

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000552150	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (May 5, 2023)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV001184428	Ambry Genetics	criteria provided, single submitter (Ambry General Variant Classification Scheme_2022)	Likely benign (Apr 30, 2018)	germline	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000552150

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(May 5, 2023)

germline

clinical testing

PubMed (1)
[See all records that cite this PMID]

SCV001184428

Ambry Genetics

criteria provided, single submitter

(Ambry General Variant Classification Scheme_2022)

Likely benign
(Apr 30, 2018)

germline

clinical testing

Citation Link

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	1	not provided	not provided	1	not provided	clinical testing

Citations

PubMed

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240-242.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Invitae, SCV000552150.8

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (1)

Description

In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant is not likely to affect RNA splicing. ClinVar contains an entry for this variant (Variation ID: 411135). This variant has not been reported in the literature in individuals affected with PRSS1-related conditions. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This sequence change affects codon 151 of the PRSS1 mRNA. It is a 'silent' change, meaning that it does not change the encoded amino acid sequence of the PRSS1 protein. It affects a nucleotide within the consensus splice site.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Ambry Genetics, SCV001184428.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	1	not provided	not provided	clinical testing	not provided

Description

This alteration is classified as likely benign based on a combination of the following: 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.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	1	not provided	not provided		1	not provided	not provided	not provided

Last Updated: Apr 20, 2024

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