ClinVar Miner

Submissions for variant NM_001312673.2(PCYT1A):c.990del (p.Ser331fs)

dbSNP: rs587777193
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Baylor-Hopkins Center for Mendelian Genomics, Johns Hopkins University School of Medicine RCV000087318 SCV000266532 pathogenic Spondylometaphyseal dysplasia-cone-rod dystrophy syndrome criteria provided, single submitter research
Labcorp Genetics (formerly Invitae), Labcorp RCV001233915 SCV001406530 uncertain significance not provided 2023-08-10 criteria provided, single submitter clinical testing This sequence change results in a frameshift in the PCYT1A gene (p.Ser331Profs*166). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 37 amino acid(s) of the PCYT1A protein and extend the protein by 128 additional amino acid residues. This variant is present in population databases (rs587777193, gnomAD 0.02%). This frameshift has been observed in individual(s) with spondylometaphyseal dysplasia with cone-rod dystrophy (PMID: 24387990). ClinVar contains an entry for this variant (Variation ID: 101061). 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.
Victorian Clinical Genetics Services, Murdoch Childrens Research Institute RCV000087318 SCV002767816 likely pathogenic Spondylometaphyseal dysplasia-cone-rod dystrophy syndrome 2019-08-28 criteria provided, single submitter clinical testing A heterozygous deletion variant was identified, NM_005017.3(PCYT1A):c.990delC in exon 10 of 10 of the PCYT1A gene. This deletion is predicted to cause a frameshift starting at position 331, introducing a stop codon 165 residues downstream, NP_005008.2(PCYT1A):p.(Ser331Profs*166). The variant is predicted to result in a loss of normal protein function through an extension of the reading frame, which is a reported mechanism of pathogenicity for this gene. The variant is present in the gnomAD population database at a frequency of 0.007% (19 heterozygotes, 0 homozygotes). It has been previously reported in patients with Spondylometaphyseal dysplasia with cone-rod dystrophy (ClinVar, Hoover-Fong, J. et al. (2014)). Other variants predicted to cause an extension of the reading frame have been reported as pathogenic in individuals with this condition (Payne, F. et al (2014)). Based on information available at the time of curation, this variant has been classified as LIKELY PATHOGENIC.
GeneDx RCV001233915 SCV005420222 likely pathogenic not provided 2024-05-28 criteria provided, single submitter clinical testing Identified in the compound heterozygous state in a patient with spondylometaphyseal dysplasia with cone-rod dystrophy in published literature (PMID: 24387990); Frameshift variant predicted to result in abnormal protein length as the last 37 amino acids are replaced with an unknown number of different amino acids as the new stop codon cannot be predicted, and other similar variants have been reported in HGMD; This variant is associated with the following publications: (PMID: 21412974, 24387990)
OMIM RCV000087318 SCV000120198 pathogenic Spondylometaphyseal dysplasia-cone-rod dystrophy syndrome 2014-01-02 no assertion criteria provided literature only

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