ClinVar Miner

Submissions for variant NM_017739.4(POMGNT1):c.880-1G>A

dbSNP: rs1317832573
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000667582 SCV000792059 likely pathogenic Muscle eye brain disease 2017-06-06 criteria provided, single submitter clinical testing
Mendelics RCV000667582 SCV001135282 likely pathogenic Muscle eye brain disease 2019-05-28 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV001855483 SCV002279823 likely pathogenic Autosomal recessive limb-girdle muscular dystrophy type 2O; Muscular dystrophy-dystroglycanopathy (congenital with intellectual disability), type B3 2022-07-12 criteria provided, single submitter clinical testing In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. ClinVar contains an entry for this variant (Variation ID: 552342). This variant has not been reported in the literature in individuals affected with POMGNT1-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change affects an acceptor splice site in intron 9 of the POMGNT1 gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in POMGNT1 are known to be pathogenic (PMID: 19299310, 20816175, 21447391, 26908613, 27391550).
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV003230564 SCV003928471 likely pathogenic Autosomal recessive limb-girdle muscular dystrophy 2023-04-05 criteria provided, single submitter clinical testing Variant summary: POMGNT1 c.880-1G>A is located in a canonical splice-site and is predicted to affect mRNA splicing resulting in a significantly altered protein due to either exon skipping, shortening, or inclusion of intronic material. Several computational tools predict a significant impact on normal splicing: Four predict the variant abolishes a canonical 3' acceptor site, with three of them also predicting the variant creates a new cryptic exonic one. However, these predictions have yet to be confirmed by functional studies. The variant was absent in 251238 control chromosomes. To our knowledge, no occurrence of c.880-1G>A in individuals affected with Limb-Girdle Muscular Dystrophy, Autosomal Recessive and no experimental evidence demonstrating its impact on protein function have been reported. Three clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 and classified the variant as likely pathogenic. Based on the evidence outlined above, the variant was classified as likely pathogenic.
Baylor Genetics RCV003459586 SCV004206002 pathogenic Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A3 2023-03-03 criteria provided, single submitter clinical testing
PreventionGenetics, part of Exact Sciences RCV004723051 SCV005340274 likely pathogenic POMGNT1-related disorder 2024-07-16 no assertion criteria provided clinical testing The POMGNT1 c.880-1G>A variant is predicted to disrupt the AG splice acceptor site and interfere with normal splicing. To our knowledge, this variant has not been reported in the literature or a large population database, indicating this variant is rare. Variants that disrupt the consensus splice acceptor site in POMGNT1 are expected to be pathogenic. This variant is interpreted as likely pathogenic.

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