NM_001312673.2(PCYT1A):c.296C>T (p.Ala99Val) AND not provided

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Feb 18, 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:: RCV002515781.2

Allele description [Variation Report for NM_001312673.2(PCYT1A):c.296C>T (p.Ala99Val)]

NM_001312673.2(PCYT1A):c.296C>T (p.Ala99Val)

Gene:

PCYT1A:phosphate cytidylyltransferase 1A, choline [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

3q29

Genomic location:

Preferred name:

NM_001312673.2(PCYT1A):c.296C>T (p.Ala99Val)

HGVS:

NC_000003.12:g.196248245G>A
NG_042817.1:g.44508C>T
NM_001312673.2:c.296C>TMANE SELECT
NM_005017.4:c.296C>T
NP_001299602.1:p.Ala99Val
NP_005008.2:p.Ala99Val
NC_000003.11:g.195975116G>A
NM_005017.2:c.296C>T
P49585:p.Ala99Val

Protein change:

A99V; ALA99VAL

Links:

UniProtKB: P49585#VAR_071084; OMIM: 123695.0001; dbSNP: rs587777189

NCBI 1000 Genomes Browser:

rs587777189

Molecular consequence:

NM_001312673.2:c.296C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_005017.4:c.296C>T - 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
SCV003525401	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Feb 18, 2022)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 30559292, 24387990, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV003525401

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Feb 18, 2022)

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

Citations

PubMed

Disease-linked mutations in the phosphatidylcholine regulatory enzyme CCTα impair enzymatic activity and fold stability.

Cornell RB, Taneva SG, Dennis MK, Tse R, Dhillon RK, Lee J.

J Biol Chem. 2019 Feb 1;294(5):1490-1501. doi: 10.1074/jbc.RA118.006457. Epub 2018 Dec 17.

PubMed [citation]

PMID:: 30559292
PMCID:: PMC6364779

Mutations in PCYT1A, encoding a key regulator of phosphatidylcholine metabolism, cause spondylometaphyseal dysplasia with cone-rod dystrophy.

Hoover-Fong J, Sobreira N, Jurgens J, Modaff P, Blout C, Moser A, Kim OH, Cho TJ, Cho SY, Kim SJ, Jin DK, Kitoh H, Park WY, Ling H, Hetrick KN, Doheny KF, Valle D, Pauli RM.

Am J Hum Genet. 2014 Jan 2;94(1):105-12. doi: 10.1016/j.ajhg.2013.11.018. No abstract available.

PubMed [citation]

PMID:: 24387990
PMCID:: PMC3882727

See all PubMed Citations (3)

Details of each submission

From Invitae, SCV003525401.2

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

Description

For these reasons, this variant has been classified as Pathogenic. Experimental studies have shown that this missense change affects PCYT1A function (PMID: 30559292). 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 expected to disrupt PCYT1A protein function. ClinVar contains an entry for this variant (Variation ID: 101057). This missense change has been observed in individual(s) with spondylometaphyseal dysplasia with cone-rod dystrophy (PMID: 24387990). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. This variant is present in population databases (rs587777189, gnomAD 0.0009%). This sequence change replaces alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 99 of the PCYT1A protein (p.Ala99Val).

#	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 14, 2024

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