Evidence Repository
The ClinGen Evidence Repository is an FDA-recognized human genetic variant database containing expert-curated assertions regarding variants' pathogenicity and supporting evidence summaries. [Disclaimer]
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Variant: NM_001142805.2:c.1205_1218del

CA2579985999

Gene: SLC6A8
Condition: creatine transporter deficiency
Inheritance Mode: X-linked inheritance
Link to MONDO
UUID: 3899813a-a2e8-4ab6-8756-478b0349a32a
Approved on: 2023-06-21
Published on: 2023-08-24

HGVS expressions

NM_001142805.2:c.1205_1218del
NC_000023.11:g.153693998_153694011del
CM000685.2:g.153693998_153694011del
NC_000023.10:g.152959453_152959466del
CM000685.1:g.152959453_152959466del
NC_000023.9:g.152612647_152612660del
NG_012016.1:g.10702_10715del
NG_012016.2:g.10702_10715del
ENST00000253122.10:c.1235_1248del
ENST00000253122.9:c.1235_1248del
ENST00000413787.1:c.258-206_258-193del
ENST00000430077.6:c.890_903del
ENST00000442457.1:c.289_302del
ENST00000457723.1:c.219_232del
ENST00000485324.1:n.1268_1281del
NM_001142805.1:c.1205_1218del
NM_001142806.1:c.890_903del
NM_005629.3:c.1235_1248del
NM_005629.4:c.1235_1248del

Pathogenic

Met criteria codes 3
PVS1 PM2_Supporting PP4_Strong

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.1235_1248del (p.Leu412GlnfsTer48) variant in SLC6A8 is a frameshift variant predicted to cause a premature stop codon, leading to nonsense mediated decay, in a gene in which loss-of-function is an established disease mechanism (PVS1). One male patient, with clinical features consistent with creatine transporter deficiency, elevated urine creatine/creatinine on one occassion, and reduced creatine peak on brain 1H-magnetic resonance spectroscopy, has been reported (PMID: 29435807) (PP4_Strong). The variant is absent in gnomad v2.1.1. (PM2_Supporting). In summary, this variant meets the criteria to be classified as pathogenic for creatine transporter deficiency. SLC6A8-specific ACMG/AMP criteria applied, as specified by the ClinGen CCDS VCEP (Specifications Version 1.1.0): PVS1, PP4_Strong, PM2_Supporting. (Classification approved by the ClinGen CCDS VCEP, June 21, 2023)
Met criteria codes
PVS1
The NM_005629.4:c.1235_1248del (p.Leu412GlnfsTer48) variant in SLC6A8 is a frameshift variant predicted to cause a premature stop codon, leading to nonsense mediated decay in a gene in which loss-of-function is an established disease mechanism (PVS1).
PM2_Supporting
The variant is absent in gnomad v2.1.1. (PM2_Supporting).
PP4_Strong
One male patient, with clinical features consistent with creatine transporter deficiency, elevated urine creatine/creatinine on one occassion, and reduced creatine peak on brain 1H-magnetic resonance spectroscopy, has been reported (PMID: 29435807) (PP4_Strong).
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