ClinVar Miner

Submissions for variant NM_001312673.2(PCYT1A):c.968dup (p.Ser323fs)

gnomAD frequency: 0.00004  dbSNP: rs587777196
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
CeGaT Center for Human Genetics Tuebingen RCV001090772 SCV001246488 pathogenic not provided 2019-03-01 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV001090772 SCV001562968 uncertain significance not provided 2022-09-01 criteria provided, single submitter clinical testing 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. ClinVar contains an entry for this variant (Variation ID: 101065). This premature translational stop signal has been observed in individual(s) with spondylometaphyseal dysplasia with cone-rod dystrophy (PMID: 24387991). It has also been observed to segregate with disease in related individuals. This variant is present in population databases (rs768195758, gnomAD 0.01%). This sequence change creates a premature translational stop signal (p.Ser323Argfs*38) in the PCYT1A gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 45 amino acid(s) of the PCYT1A protein.
Neuberg Centre For Genomic Medicine, NCGM RCV000087322 SCV005373638 uncertain significance Spondylometaphyseal dysplasia-cone-rod dystrophy syndrome 2023-05-20 criteria provided, single submitter clinical testing The frameshift variant c.968dup(p.Ser323ArgfsTer38) in PCYT1A gene has been observed in homozygous state in individual(s) with spondylometaphyseal dysplasia with cone-rod dystrophy (Yamamoto et. al., 2014). It has also been observed to segregate with disease in related individuals (Yamamoto et. al., 2014). The observed variant has allele frequency of 0.0005% in gnomAD exomes database. This variant has been submitted to the ClinVar database as Pathogenic / Uncertain Significance (VUS). This variant causes a frameshift starting with codon Serine 323, changes this amino acid to Arginine residue, and creates a premature Stop codon at position 38 of the new reading frame, denoted p.Ser323ArgfsTer38. Loss of function variants have been previously reported to be disease causing. However since this variant is present in the last exon, functional studies will be required to prove protein truncation. Hence the variant is classified as Uncertain Significance.
OMIM RCV000087322 SCV000120202 pathogenic Spondylometaphyseal dysplasia-cone-rod dystrophy syndrome 2014-01-02 no assertion criteria provided literature only

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