Submissions for variant NM_080424.4(SP110):c.584-10C>G

gnomAD frequency: 0.00188  dbSNP: rs148591984

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Illumina Laboratory Services, Illumina	RCV000344535	SCV000428340	likely benign	Hepatic veno-occlusive disease-immunodeficiency syndrome	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 and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease.
Labcorp Genetics (formerly Invitae), Labcorp	RCV000344535	SCV000763944	benign	Hepatic veno-occlusive disease-immunodeficiency syndrome	2025-01-26	criteria provided, single submitter	clinical testing
Center for Genomics, Ann and Robert H. Lurie Children's Hospital of Chicago	RCV001281000	SCV001468396	uncertain significance	Hepatic veno-occlusive disease-immunodeficiency syndrome; Mycobacterium tuberculosis, susceptibility to	2021-03-30	criteria provided, single submitter	clinical testing	SP110 NM_004509.3 exon 5 c.584-10C>G: This variant has not been reported in the literature but is present in 0.3% (446/128970) of European alleles in the Genome Aggregation Database (https://gnomad.broadinstitute.org/variant/2-231077155-G-C?dataset=gnomad_r2_1). This variant is present in ClinVar (Variation ID:334913). Evolutionary conservation and computational predictive tools for this variant are limited or unavailable. This variant is an intronic variant with no predicted change in the amino acid sequence but may have an unknown effect on splicing. Further studies are needed to understand its impact. In summary, data on this variant is insufficient for disease classification. Therefore, the clinical significance of this variant is uncertain.
Genome Diagnostics Laboratory, University Medical Center Utrecht	RCV001706546	SCV001929801	likely benign	not provided		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV001706546	SCV001970595	likely benign	not provided		no assertion criteria provided	clinical testing
PreventionGenetics, part of Exact Sciences	RCV003969964	SCV004783974	likely benign	SP110-related disorder	2023-10-16	no assertion criteria provided	clinical testing	This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).