NM_006907.4(PYCR1):c.769G>A (p.Ala257Thr) AND not provided

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

Germline classification:: Uncertain significance (2 submissions)
Last evaluated:: Oct 13, 2023
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:: RCV000059740.4

Allele description

NM_006907.4(PYCR1):c.769G>A (p.Ala257Thr)

Gene:

PYCR1:pyrroline-5-carboxylate reductase 1 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

17q25.3

Genomic location:

Preferred name:

NM_006907.4(PYCR1):c.769G>A (p.Ala257Thr)

HGVS:

NC_000017.11:g.81934354C>T
NG_023032.1:g.7739G>A
NM_001282279.2:c.676G>A
NM_001282280.2:c.769G>A
NM_001282281.2:c.850G>A
NM_001330523.2:c.633+299G>A
NM_006907.4:c.769G>AMANE SELECT
NM_153824.3:c.769G>A
NP_001269208.1:p.Ala226Thr
NP_001269209.1:p.Ala257Thr
NP_001269210.1:p.Ala284Thr
NP_008838.2:p.Ala257Thr
NP_722546.1:p.Ala257Thr
NC_000017.10:g.79892230C>T
NM_006907.2:c.769G>A
P32322:p.Ala257Thr

Protein change:

A226T; ALA257THR

Links:

UniProtKB: P32322#VAR_059075; UniProtKB/Swiss-Prot: VAR_059075; OMIM: 179035.0010; dbSNP: rs281875318

NCBI 1000 Genomes Browser:

rs281875318

Molecular consequence:

NM_001330523.2:c.633+299G>A - intron variant - [Sequence Ontology: SO:0001627]
NM_001282279.2:c.676G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001282280.2:c.769G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001282281.2:c.850G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_006907.4:c.769G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_153824.3:c.769G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000091310	UniProtKB/Swiss-Prot	no classification provided	not provided	not provided	not provided	PubMed (1) [See all records that cite this PMID]
SCV002216897	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Oct 13, 2023)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 19648921, 30450527, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000091310

UniProtKB/Swiss-Prot

no classification provided

not provided

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

SCV002216897

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Oct 13, 2023)

germline

clinical testing

PubMed (3)
[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
not provided	not provided	not provided	not provided	not provided	not provided	1	not provided	literature only

Citations

PubMed

Mutations in PYCR1 cause cutis laxa with progeroid features.

Reversade B, Escande-Beillard N, Dimopoulou A, Fischer B, Chng SC, Li Y, Shboul M, Tham PY, Kayserili H, Al-Gazali L, Shahwan M, Brancati F, Lee H, O'Connor BD, Schmidt-von Kegler M, Merriman B, Nelson SF, Masri A, Alkazaleh F, Guerra D, Ferrari P, Nanda A, et al.

Nat Genet. 2009 Sep;41(9):1016-21. doi: 10.1038/ng.413. Epub 2009 Aug 2. Erratum in: Nat Genet. 2022 Feb;54(2):213. doi: 10.1038/s41588-022-01013-2.

PubMed [citation]

PMID:: 19648921

Analyses of LMNA-negative juvenile progeroid cases confirms biallelic POLR3A mutations in Wiedemann-Rautenstrauch-like syndrome and expands the phenotypic spectrum of PYCR1 mutations.

Lessel D, Ozel AB, Campbell SE, Saadi A, Arlt MF, McSweeney KM, Plaiasu V, Szakszon K, Szőllős A, Rusu C, Rojas AJ, Lopez-Valdez J, Thiele H, Nürnberg P, Nickerson DA, Bamshad MJ, Li JZ, Kubisch C, Glover TW, Gordon LB.

Hum Genet. 2018 Dec;137(11-12):921-939. doi: 10.1007/s00439-018-1957-1. Epub 2018 Nov 19.

PubMed [citation]

PMID:: 30450527
PMCID:: PMC6652186

See all PubMed Citations (3)

Details of each submission

From UniProtKB/Swiss-Prot, SCV000091310.1

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

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

From Invitae, SCV002216897.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

Description

This sequence change replaces alanine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 257 of the PYCR1 protein (p.Ala257Thr). This variant is present in population databases (rs281875318, gnomAD 0.01%). This missense change has been observed in individuals with cutis laxa (PMID: 19648921, 30450527). ClinVar contains an entry for this variant (Variation ID: 29863). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt PYCR1 protein function. 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.

#	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: Feb 20, 2024

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