ClinVar Miner

Submissions for variant NM_005629.4(SLC6A8):c.644+9G>A

dbSNP: rs200353790
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 2
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ClinGen Cerebral Creatine Deficiency Syndromes Variant Curation Expert Panel, ClinGen RCV000459921 SCV003852675 likely benign Creatine transporter deficiency 2023-01-12 reviewed by expert panel curation The NM_005629.4:c.644+9G>A variant in SLC6A8 is in the region of the donor splice site of intron 3. This variant was reported in a female patient with intellectual disability (LOVD, https://databases.lovd.nl/shared/genes/SLC6A8; individual #00185850) but details of biochemical testing or brain MRS are not available (PMID: 20717164). The computational splicing predictors SpliceAI and varSEAK suggest that the variant has no impact on splicing (BP4). This is also supported by the reported results of 5 different predictors (Netgene2, Fruitfly (i.e. NNSplice), Splice predictor, Genscan W, FSplice) (PMID 20717164). PhyloP100 way score for this intronic variant is 0.35, which is below the threshols of 2.0, indicating that this nucleotide is not highly conserved (BP7). The highest population minor allele frequency in gnomAD v2.1.1 is 0.0001061 in the African population. This allele frequency is between the ClinGen CCDS VCEP’s allele frequency thresholds for PM2 (<0.00002) and BS1 (>0.0002). Therefore, neither code is met. There is a ClinVar entry for this variant (Variation ID: 416004) In summary, this variant meets the criteria to be classified as likely benign for X-linked creatine transporter deficiency. SLC6A8-specific ACMG/AMP criteria applied, as specified by the ClinGen CCDS VCEP (Specifications verion 1.1.0): BP4. BP7. This classification was approved by the ClinGen CCDS VCEP on Jan 12, 2023).
Invitae RCV000459921 SCV000561169 likely benign Creatine transporter deficiency 2023-12-08 criteria provided, single submitter clinical testing

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.