ClinVar Miner

Submissions for variant NM_020461.4(TUBGCP6):c.741+1G>A

dbSNP: rs1460482736
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Lifecell International Pvt. Ltd RCV003232911 SCV003929437 likely pathogenic Microcephaly and chorioretinopathy 1 criteria provided, single submitter clinical testing A Heterozygous Intron, Splice site donor variant c.741+1G>A in Exon 1 of the TUBGCP6 gene that results in the amino acid substitution was identified. The observed variant novel in gnomAD exomes and genomes, respectively. The severity of the impact of this variant on the protein is high, based on the effect of the protein and REVEL score . Rare Exome Variant Ensemble Learner (REVEL) is an ensembl method for predicting the pathogenicity of missense variants based on a combination of scores from 13 individual tools: MutPred, FATHMM v2.3, VEST 3.0, PolyPhen-2, SIFT, PROVEAN, MutationAssessor, MutationTaster, LRT, GERP++, SiPhy, phyloP, and phastCons. The REVEL score for an individual missense variant can range from 0 to 1, with higher scores reflecting greater likelihood that the variant is disease-causing. Based on the above evidence this variant has been classified as Likely Pathogenic according to the ACMG guidelines.
Labcorp Genetics (formerly Invitae), Labcorp RCV005102458 SCV005746305 likely pathogenic not provided 2024-03-07 criteria provided, single submitter clinical testing This sequence change affects a donor splice site in intron 1 of the TUBGCP6 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 TUBGCP6 are known to be pathogenic (PMID: 25344692). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with TUBGCP6-related conditions. ClinVar contains an entry for this variant (Variation ID: 2504122). 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 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.

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