Submissions for variant NM_004551.3(NDUFS3):c.381+6T>C

gnomAD frequency: 0.00035  dbSNP: rs377579231

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Illumina Laboratory Services, Illumina	RCV000332963	SCV000372512	uncertain significance	Leigh syndrome	2018-01-12	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, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
Illumina Laboratory Services, Illumina	RCV000389911	SCV000372513	uncertain significance	Mitochondrial complex I deficiency, nuclear type 1	2018-01-12	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, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
Invitae	RCV001859811	SCV002268013	uncertain significance	not provided	2022-01-23	criteria provided, single submitter	clinical testing	This sequence change falls in intron 4 of the NDUFS3 gene. It does not directly change the encoded amino acid sequence of the NDUFS3 protein. It affects a nucleotide within the consensus splice site. This variant is present in population databases (rs377579231, gnomAD 0.09%). This variant has been observed in individual(s) with Leigh syndrome (PMID: 33097395). ClinVar contains an entry for this variant (Variation ID: 304996). Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Studies have shown that this variant is associated with altered splicing, but the impact on the resulting protein product is unknown (PMID: 33097395). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Revvity Omics, Revvity	RCV001374465	SCV003813535	uncertain significance	Mitochondrial complex 1 deficiency, nuclear type 8	2021-12-02	criteria provided, single submitter	clinical testing
OMIM	RCV001374465	SCV001571417	pathogenic	Mitochondrial complex 1 deficiency, nuclear type 8	2021-04-16	no assertion criteria provided	literature only