ClinVar Miner

Submissions for variant NM_133259.4(LRPPRC):c.1369+5G>A

gnomAD frequency: 0.00003  dbSNP: rs199628926
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Illumina Laboratory Services, Illumina RCV000667137 SCV000430623 uncertain significance Congenital lactic acidosis, Saguenay-Lac-Saint-Jean type 2018-01-13 criteria provided, single submitter clinical testing This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
Counsyl RCV000667137 SCV000791542 uncertain significance Congenital lactic acidosis, Saguenay-Lac-Saint-Jean type 2017-05-12 criteria provided, single submitter clinical testing
Invitae RCV002523133 SCV003449863 uncertain significance not provided 2022-06-27 criteria provided, single submitter clinical testing This sequence change falls in intron 11 of the LRPPRC gene. It does not directly change the encoded amino acid sequence of the LRPPRC protein. It affects a nucleotide within the consensus splice site. This variant is present in population databases (rs199628926, gnomAD 0.002%). This variant has not been reported in the literature in individuals affected with LRPPRC-related conditions. ClinVar contains an entry for this variant (Variation ID: 336164). 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. 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.
Ambry Genetics RCV003352843 SCV004070747 uncertain significance Inborn genetic diseases 2023-07-03 criteria provided, single submitter clinical testing The c.1369+5G>A intronic alteration consists of a G to A substitution 5 nucleotides after exon 11 (coding exon 11) in the LRPPRC gene. Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.

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