NM_022356.4(P3H1):c.2099del (p.Pro700fs) AND Osteogenesis imperfecta type 8

This record was updated by the submitter. Please see the current version.

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Dec 29, 2022
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

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:: RCV003601646.1

Allele description

NM_022356.4(P3H1):c.2099del (p.Pro700fs)

Gene:

P3H1:prolyl 3-hydroxylase 1 [Gene - OMIM - HGNC]

Variant type:

Deletion

Cytogenetic location:

1p34.2

Genomic location:

Preferred name:

NM_022356.4(P3H1):c.2099del (p.Pro700fs)

HGVS:

NC_000001.11:g.42746811del
NG_008123.1:g.25276del
NM_001146289.2:c.*24del
NM_001243246.2:c.*103del
NM_022356.4:c.2099delMANE SELECT
NP_071751.3:p.Pro700Glnfs
NP_071751.3:p.Pro700fs
LRG_5t1:c.2097del
LRG_5t2:c.*22del
LRG_5t3:c.*101del
LRG_5:g.25276del
LRG_5p1:p.Pro700Glnfs
NC_000001.10:g.43212480del
NC_000001.10:g.43212482del
NM_001146289.1:c.*22delC
NM_001243246.1:c.*101delC
NM_022356.2:c.*101delC
NM_022356.3:c.2097delC

Protein change:

P700fs

Molecular consequence:

NM_001146289.2:c.*24del - 3 prime UTR variant - [Sequence Ontology: SO:0001624]
NM_001243246.2:c.*103del - 3 prime UTR variant - [Sequence Ontology: SO:0001624]
NM_022356.4:c.2099del - frameshift variant - [Sequence Ontology: SO:0001589]

Condition(s)

Name:: Osteogenesis imperfecta type 8 (OI8)
Synonyms:: OI type VIII
Identifiers:: MONDO: MONDO:0012581; MedGen: C1970458; OMIM: 610915

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004487695	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Dec 29, 2022)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 22615817, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004487695

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Dec 29, 2022)

germline

clinical testing

PubMed (2)
[See all records that cite these PMIDs]

Help

Summary from all submissions

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

Citations

PubMed

A novel mutation in LEPRE1 that eliminates only the KDEL ER- retrieval sequence causes non-lethal osteogenesis imperfecta.

Takagi M, Ishii T, Barnes AM, Weis M, Amano N, Tanaka M, Fukuzawa R, Nishimura G, Eyre DR, Marini JC, Hasegawa T.

PLoS One. 2012;7(5):e36809. doi: 10.1371/journal.pone.0036809. Epub 2012 May 15.

PubMed [citation]

PMID:: 22615817
PMCID:: PMC3352923

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. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Invitae, SCV004487695.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

Description

For these reasons, this variant has been classified as Pathogenic. This variant disrupts a region of the P3H1 protein in which other variant(s) (p.Glu719Argfs*11) have been determined to be pathogenic (PMID: 22615817; Invitae). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. This variant has not been reported in the literature in individuals affected with P3H1-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change results in a frameshift in the P3H1 gene (p.Pro700Glnfs*48). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 37 amino acid(s) of the P3H1 protein and extend the protein by 10 additional amino acid residues.

#	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

Last Updated: Sep 1, 2024

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