The ClinGen Evidence Repository is an FDA-recognized human genetic variant database containing expert-curated assertions regarding variants' pathogenicity and supporting evidence summaries. [Disclaimer]
  • Gene obtained from curated document aligns with the Allele Registry but not with ClinVar data
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Variant: NM_005629.4(SLC6A8):c.340C>A (p.Gln114Lys)

CA415077728

561109 (ClinVar)

Gene: SLC6A8
Condition: creatine transporter deficiency
Inheritance Mode: X-linked inheritance
UUID: be737472-5138-4984-ab23-ec3d5826e786
Approved on: 2024-06-13
Published on: 2024-06-24

HGVS expressions

NM_005629.4:c.340C>A
NM_005629.4(SLC6A8):c.340C>A (p.Gln114Lys)
NC_000023.11:g.153690452C>A
CM000685.2:g.153690452C>A
NC_000023.10:g.152955907C>A
CM000685.1:g.152955907C>A
NC_000023.9:g.152609101C>A
NG_012016.1:g.7156C>A
NG_012016.2:g.7156C>A
ENST00000253122.10:c.340C>A
ENST00000675713.1:n.94C>A
ENST00000253122.9:c.340C>A
ENST00000430077.6:c.-6C>A
ENST00000476466.1:n.192C>A
NM_001142805.1:c.340C>A
NM_001142806.1:c.-6C>A
NM_005629.3:c.340C>A
NM_001142805.2:c.340C>A
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Uncertain Significance

Met criteria codes 4
PP4 PP3 PM5_Supporting PM2_Supporting

Evidence Links 0

Expert Panel

Criteria Specification Information

Criteria Specification: ClinGen Cerebral Creatine Deficiency Syndromes Expert Panel Specifications to the ACMG/AMP Variant Interpretation Guidelines for SLC6A8 Version 1.1.0

Criteria Specification Approval History
Criteria Specifications for this VCEP
Evidence submitted by expert panel
Cerebral Creatine Deficiency Syndromes VCEP
The NM_005629.4:c.340C>A in SLC6A8 is predicted to result in substitution of glutamine by lysine at amino acid 114 (p.Gln114Lys). One male patient with clinical features and urine creatine results consistent with creatine transporter deficiency has been reported (PMID: 25326635, ClinVar SCV000807540.2, Association for Creatine Deficiencies registry) (PP4). The computational predictor REVEL gives a score of 0.918 which is above the threshold of 0.75, evidence that correlates with impact to SLC6A8 function (PP3). This variant is not in gnomAD v2.1.1 or v4.1.0. (PM2_Supporting). Another amino acid change at the same position, c.342G>C (p.Gln114His) (ClinVar Variation ID: 940774) has been classified as likely pathogenic by the ClinGen CCDS VCEP (PM5_Supporting). In summary, this variant meets the criteria to be classified as a variant of uncertain significance for creatine transporter deficiency. SLC6A8-specification ACMG/AMP criteria applied, as specified by the ClinGen Cerebral Creatine Deficiency Syndromes Variant Curation Expert Panel (Specifications Version v1.1.0): PP3, PP4, PM2_Supporting, PM5_Supporting. (Classification approved by the ClinGen CCDS VCEP on June 13, 2024)
Met criteria codes
PP4
One male patient with clinical features and urine creatine results consistent with creatine transporter deficiency has been reported (PMID: 25326635, ClinVar SCV000807540.2, data from the ACD registry) (PP4).
PP3
The computational predictor REVEL gives a score of 0.918 which is above the threshold of 0.75, evidence that correlates with impact to SLC6A8 function (PP3). SpliceAI predicts that the variant has no impact on splicing.
PM5_Supporting
Another amino acid change at the same position, c.342G>C (p.Gln114His) (ClinVar Variation ID: 940774) has been classified as likely pathogenic by the ClinGen CCDS VCEP (PM5_Supporting).
PM2_Supporting
This variant is not in gnomAD v2.1.1. (PM2_Supporting).
Curation History
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