ClinVar Miner

Submissions for variant NM_006019.4(TCIRG1):c.117+4A>C

dbSNP: rs751881962
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Myriad Genetics, Inc. RCV001810546 SCV002060129 uncertain significance Autosomal recessive osteopetrosis 1 2021-11-03 criteria provided, single submitter clinical testing NM_006019.3(TCIRG1):c.117+4A>C is an intronic variant classified as a variant of uncertain significance in the context of autosomal recessive osteopetrosis type 1. c.117+4A>C has been observed in cases with relevant disease (PMID: 30537558). Functional assessments of this variant are not available in the literature. c.117+4A>C has been observed in population frequency databases (gnomAD: SAS 0.03%). In summary, there is insufficient evidence to classify NM_006019.3(TCIRG1):c.117+4A>C as pathogenic or benign. Please note: this variant was assessed in the context of healthy population screening.
Invitae RCV001885295 SCV002232458 pathogenic not provided 2023-11-17 criteria provided, single submitter clinical testing This sequence change falls in intron 2 of the TCIRG1 gene. It does not directly change the encoded amino acid sequence of the TCIRG1 protein. It affects a nucleotide within the consensus splice site. This variant is present in population databases (rs751881962, gnomAD 0.03%). This variant has been observed in individual(s) with TCIRG1-related conditions (PMID: 30537558). 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: 1334165). 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. This variant disrupts the c.117+4 nucleotide in the TCIRG1 gene. Other variant(s) that disrupt this nucleotide have been determined to be pathogenic (PMID: 10942435, 15300850, 19507210, 24989235). This suggests that this nucleotide is clinically significant, and that variants that disrupt this position are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic.
Baylor Genetics RCV001810546 SCV004205785 likely pathogenic Autosomal recessive osteopetrosis 1 2023-04-17 criteria provided, single submitter clinical testing

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