Submissions for variant NM_001079866.2(BCS1L):c.441C>T (p.Phe147=)

dbSNP: rs2106324466

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV001844327	SCV005380817	likely pathogenic	GRACILE syndrome	2024-08-08	criteria provided, single submitter	clinical testing	Variant summary: BCS1L c.441C>T alters a conserved nucleotide resulting in a synonymous change. Several computational tools predict a significant impact on normal splicing: Two predict the variant no significant impact on splicing. One predict the variant weakens a 5' donor site. Two predict the variant strengthens a cryptic 5' donor site. At least one publication reports experimental evidence that this variant affects mRNA splicing (Shamseldin_2021). The variant was absent in 251444 control chromosomes. c.441C>T has been reported in the literature in individuals affected with GRACILE Syndrome (Shamseldin_2021, Maddirevula_2020). These data indicate that the variant is likely to be associated with disease. The following publications have been ascertained in the context of this evaluation (PMID: 32552793, 34645488). ClinVar contains an entry for this variant (Variation ID: 1252010). Based on the evidence outlined above, the variant was classified as likely pathogenic.
Genomic Medicine Center of Excellence, King Faisal Specialist Hospital and Research Centre	RCV004813180	SCV005438283	likely pathogenic	Mitochondrial complex III deficiency nuclear type 1	2024-12-18	criteria provided, single submitter	clinical testing
Genomic Medicine Center of Excellence, King Faisal Specialist Hospital and Research Centre	RCV001844327	SCV001870446	pathogenic	GRACILE syndrome	2021-04-29	no assertion criteria provided	research