ClinVar Miner

Submissions for variant NM_000263.4(NAGLU):c.507_516del (p.Ser169fs) (rs483352897)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Centre for Mendelian Genomics,University Medical Centre Ljubljana RCV000626637 SCV000747339 pathogenic Hypertrichosis; Abnormality of metabolism/homeostasis; Coarse facial features; Abnormal facial shape; Thick eyebrow; Hepatosplenomegaly; Mucopolysacchariduria; Intellectual disability, severe 2017-01-01 criteria provided, single submitter clinical testing
Invitae RCV001047802 SCV001211783 pathogenic Mucopolysaccharidosis, MPS-III-B; Charcot-Marie-Tooth disease, axonal type 2V 2020-05-20 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Ser169Argfs*13) in the NAGLU gene. It is expected to result in an absent or disrupted protein product. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the ExAC database. This variant has been observed in an individual affected with Sanfilippo syndrome type B (PMID: 8650226). This variant is also known in the literature as 503del10. Loss-of-function variants in NAGLU are known to be pathogenic (PMID: 9832037, 10094189, 16151907). For these reasons, this variant has been classified as Pathogenic.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000001630 SCV001623317 pathogenic Mucopolysaccharidosis, MPS-III-B 2021-04-23 criteria provided, single submitter clinical testing Variant summary: NAGLU c.507_516del10 (p.Ser169ArgfsX13) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. The variant allele was found at a frequency of 1.2e-05 in 251134 control chromosomes (gnomAD). c.507_516del10 (also known as 503del10 in the literature) has been reported in the literature in multiple individuals (both homozygous and compound heterozygous) affected with Mucopolysaccharidosis Type IIIB (Sanfilippo Syndrome B) (example: Beesley_2004, Weber_1999, Zhao_1998) . These data indicate that the variant is very likely to be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Two ClinVar submitters (evaluation after 2014) cite the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic.
GeneDx RCV001588794 SCV001816601 pathogenic not provided 2021-02-10 criteria provided, single submitter clinical testing Frameshift variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; Not observed at a significant frequency in large population cohorts (Lek et al., 2016); This variant is associated with the following publications: (PMID: 8650226)
OMIM RCV000001630 SCV000021786 pathogenic Mucopolysaccharidosis, MPS-III-B 1996-06-11 no assertion criteria provided literature only

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