ClinVar Miner

Submissions for variant NM_176787.5(PIGN):c.1434+5G>A

gnomAD frequency: 0.00001  dbSNP: rs369486176
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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
CeGaT Center for Human Genetics Tuebingen RCV001091656 SCV001247828 likely pathogenic not provided 2019-10-01 criteria provided, single submitter clinical testing
Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen RCV001091656 SCV001448043 likely pathogenic not provided 2020-10-23 criteria provided, single submitter clinical testing
Institute for Genomic Statistics and Bioinformatics, University Hospital Bonn RCV000250290 SCV001519383 pathogenic Multiple congenital anomalies-hypotonia-seizures syndrome 1 criteria provided, single submitter clinical testing The NM_176787:exon17:c.1434+5G>A splice site mutation is a known pathogenic variant that has been maternally inherited.
Invitae RCV000250290 SCV001576043 pathogenic Multiple congenital anomalies-hypotonia-seizures syndrome 1 2024-01-28 criteria provided, single submitter clinical testing This sequence change falls in intron 16 of the PIGN gene. It does not directly change the encoded amino acid sequence of the PIGN protein. It affects a nucleotide within the consensus splice site. This variant is present in population databases (rs369486176, gnomAD 0.004%). This variant has been observed in individual(s) with PIGN-related conditions (PMID: 26394714, 34051595, 35179230). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 264636). Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic.
GeneDx RCV001091656 SCV001813893 likely pathogenic not provided 2021-06-29 criteria provided, single submitter clinical testing In silico analysis, which includes splice predictors and evolutionary conservation, supports that this variant does not alter protein structure/function; Not observed at a significant frequency in large population cohorts (Lek et al., 2016); This variant is associated with the following publications: (PMID: 31589614, 34051595, 27535533, 27038415, 26394714)
Neuberg Supratech Reference Laboratories Pvt Ltd, Neuberg Centre for Genomic Medicine RCV000250290 SCV004100637 likely pathogenic Multiple congenital anomalies-hypotonia-seizures syndrome 1 criteria provided, single submitter clinical testing The splice region variant c.1434+5G>A in PIGN (NM_176787.5) has been reported previously in affected indivduals (Fleming L et al). The variant as been submitted to ClinVar as Likely Pathogenic. The c.1434+5G>A variant is observed in 1/28,292 (0.0035%) alleles from individuals of South Asian background in gnomAD Exomes and is novel (not in any individuals) in 1000 Genomes. The nucleotide c.1434+5G>A in PIGN is predicted conserved by GERP++ and PhyloP across 100 vertebrates. For these reasons, this variant has been classified as Likely Pathogenic.
OMIM RCV000250290 SCV000320693 pathogenic Multiple congenital anomalies-hypotonia-seizures syndrome 1 2016-09-28 no assertion criteria provided literature only

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