Total submissions: 6
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Clin |
RCV001088436 | SCV002600177 | benign | Creatine transporter deficiency | 2022-06-06 | reviewed by expert panel | curation | The NM_005629.4:c.544G>A variant in SLC6A8 is a missense variant predicted to cause substitution of valine by methionine at amino acid 182 (p.Val182Met). The highest population minor allele frequency in gnomAD v2.1.1 is 0.00084 (16/19086 alleles) in the African/African American population, meeting the CCDS VCEP’s allele frequency threshold for BS1 (>0.0002) (BS1). This variant is present in 5 or more hemizygotes in gnomAD v2.1.1 (BS2). Furthermore, the variant did not segregate with intellectual disability in multiple brothers, and the proband with the variant had normal urine creatine and normal cerebral creatine on 1H-magnetic resonance spectroscopy (PMID 16738945). The computational predictor REVEL gives a score of 0.184, evidence that does not predict a damaging effect on SLC6A8 function, and SpliceAI predicts no impact of the variant on splicing (BP4). There is a ClinVar entry for this variant (Variation ID: 465147). In summary, this variant meets the criteria to be classified as benign for creatine transporter deficiency. SLC6A8-specific ACMG/AMP codes met, as specified by the ClinGen CCDS VCEP (Specifications Version 1.1.0): BS1, BS2, BP4. (Classification approved by the ClinGen CCDS VCEP on June 6, 2022). |
Invitae | RCV001088436 | SCV000640033 | benign | Creatine transporter deficiency | 2024-01-29 | criteria provided, single submitter | clinical testing | |
Gene |
RCV000713356 | SCV000719016 | likely benign | not provided | 2020-06-30 | criteria provided, single submitter | clinical testing | This variant is associated with the following publications: (PMID: 16738945) |
Athena Diagnostics Inc | RCV000713356 | SCV000843954 | uncertain significance | not provided | 2018-04-24 | criteria provided, single submitter | clinical testing | |
Genome Diagnostics Laboratory, |
RCV000713356 | SCV001932057 | likely benign | not provided | no assertion criteria provided | clinical testing | ||
Clinical Genetics DNA and cytogenetics Diagnostics Lab, |
RCV000713356 | SCV001966321 | likely benign | not provided | no assertion criteria provided | clinical testing |