ClinVar Miner

Submissions for variant NM_005629.4(SLC6A8):c.1162G>A (p.Ala388Thr)

gnomAD frequency: 0.00032  dbSNP: rs374163604
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 7
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 RCV000640937 SCV003852677 benign Creatine transporter deficiency 2023-02-23 reviewed by expert panel curation The NM_005629.4(SLC6A8):c.1162G>A (p.Ala388Thr) variant in SLC6A8 is a missense variant predicted to cause substitution of Threonine for Alanine at amino acid 338 (p.Ala338Thr). There is a ClinVar entry for this variant (Variation ID:436771). This variant is found with an allele frequency of 0.003854 in gnomADv2.1.1 with 17 hemizygotes present in that population database. Given the presence of >10 hemizygotes in gnomADv2.1.1 and an allele frequency >0.002, the stand alone benign criteria BA1 is applicable for this variant. In summary, this variant meets the criteria to be classified as Benign for Creatine Transporter Deficiency based on the ACMG/AMP criteria applied, as specified by the ClinGen Cerebral Creatine Deficiency Syndromes Variant Curation Expert Panel (Specifications Version 1.1.0; ; classification approved Feb 23, 2023): BA1
Genetic Services Laboratory, University of Chicago RCV000499651 SCV000597120 uncertain significance not specified 2016-02-22 criteria provided, single submitter clinical testing
Invitae RCV000640937 SCV000762542 benign Creatine transporter deficiency 2024-01-25 criteria provided, single submitter clinical testing
CeGaT Center for Human Genetics Tuebingen RCV001092998 SCV001249763 likely benign not provided 2023-08-01 criteria provided, single submitter clinical testing SLC6A8: PP2, BS2
GeneDx RCV001092998 SCV001824487 likely benign not provided 2021-03-03 criteria provided, single submitter clinical testing In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; Previously reported as a non-pathogenic variant in a male with intellectual disability and normal creatine uptake in cultured skin fibroblasts (Betsalel et al, 2011).; This variant is associated with the following publications: (PMID: 28758966, 22281021, 26684475, 20717164, 25861866)
Ambry Genetics RCV002323868 SCV002626263 benign Inborn genetic diseases 2019-11-05 criteria provided, single submitter clinical testing This alteration is classified as benign based on a combination of the following: population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
Natera, Inc. RCV001834620 SCV002084559 likely benign Creatine deficiency syndrome 1 2020-01-24 no assertion criteria provided 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.