Submissions for variant NM_000387.6(SLC25A20):c.198+2T>C

gnomAD frequency: 0.00022  dbSNP: rs147540030

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV001204864	SCV001376091	likely pathogenic	Carnitine acylcarnitine translocase deficiency	2023-10-27	criteria provided, single submitter	clinical testing	This sequence change affects a donor splice site in intron 2 of the SLC25A20 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 SLC25A20 are known to be pathogenic (PMID: 25614308). This variant is present in population databases (rs147540030, gnomAD 0.06%). This variant has not been reported in the literature in individuals affected with SLC25A20-related conditions. ClinVar contains an entry for this variant (Variation ID: 936127). 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.
Fulgent Genetics, Fulgent Genetics	RCV001204864	SCV002808925	likely pathogenic	Carnitine acylcarnitine translocase deficiency	2021-10-07	criteria provided, single submitter	clinical testing
Baylor Genetics	RCV001204864	SCV003835661	likely pathogenic	Carnitine acylcarnitine translocase deficiency	2024-03-22	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV001204864	SCV004804410	likely pathogenic	Carnitine acylcarnitine translocase deficiency	2024-01-11	criteria provided, single submitter	clinical testing	Variant summary: SLC25A20 c.198+2T>C is located in a canonical splice-site and is predicted to affect mRNA splicing resulting in a significantly altered protein due to either exon skipping, shortening, or inclusion of intronic material. Several computational tools predict a significant impact on normal splicing: three predict the variant abolishes a 5' splicing donor site. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 3.2e-05 in 251492 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.198+2T>C in individuals affected with Carnitine-Acylcarnitine Translocase Deficiency and no experimental evidence demonstrating its impact on protein function have been reported. ClinVar contains an entry for this variant (Variation ID: 936127). Based on the evidence outlined above, the variant was classified as likely pathogenic.
PreventionGenetics, part of Exact Sciences	RCV004757381	SCV005348754	likely pathogenic	SLC25A20-related disorder	2024-09-10	no assertion criteria provided	clinical testing	The SLC25A20 c.198+2T>C variant is predicted to disrupt the GT donor site and interfere with normal splicing. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.056% of alleles in individuals of African descent in gnomAD. Variants that disrupt the consensus splice donor site in SLC25A20 are expected to be pathogenic. This variant is interpreted as likely pathogenic.