ClinVar Miner

Submissions for variant NM_005629.4(SLC6A8):c.1285C>G (p.Leu429Val)

gnomAD frequency: 0.00003  dbSNP: rs782551106
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ClinGen Cerebral Creatine Deficiency Syndromes Variant Curation Expert Panel, ClinGen RCV000887630 SCV003852678 likely benign Creatine transporter deficiency 2023-02-23 reviewed by expert panel curation The NM_005629.4(SLC6A8):c.1285C>G (p.Leu429Val) variant in SLC6A8 is a missense variant predicted to cause substitution of Valine for Leucine at amino acid 429 (p.Leu429Val). There is a ClinVar entry for this variant (Variation ID:715196, conflicting interpretations) with classifications as Variant of Uncertain Significance (n=1), Likely Benign (n=1), and Benign (n=1). This variant is found with an allele frequency of 0.00004401 in gnomADv2.1.1 with 5 hemizygotes present in that population database. Given the presence of 5 hemizygotes in gnomADv2.1.1, BS1 is applicable for this variant. The computational predictor REVEL gives a score of 0.101 which is below the threshold of 0.20, suggesting a benign effect of this variant on protein function, therefore BP4 criteria is applicable. At the time of this curation, this variant has not been reported in affected individuals in the literature. In summary, this variant meets the criteria to be classified as Likely 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): BS1, BP4 (Classification approved by the ClinGen CCDS VCEP on February 23, 2023).
Invitae RCV000887630 SCV001031201 benign Creatine transporter deficiency 2024-01-27 criteria provided, single submitter clinical testing
CeGaT Center for Human Genetics Tuebingen RCV001092999 SCV001249765 uncertain significance not provided 2019-07-01 criteria provided, single submitter clinical testing
GeneDx RCV001092999 SCV002601248 uncertain significance not provided 2022-11-03 criteria provided, single submitter clinical testing In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
Ambry Genetics RCV002539369 SCV003742694 likely benign Inborn genetic diseases 2021-11-15 criteria provided, single submitter clinical testing This alteration is classified as likely 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. RCV001830943 SCV002084564 likely benign Creatine deficiency syndrome 1 2020-04-11 no assertion criteria provided clinical testing

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