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]
Link to SEPIO compliant JSON-LD document
  • No ClinVar Id was directly found from the curated document
  • No CSPEC related information was provided by the message!
  • See Evidence submitted by expert panel for details.

Variant: NM_001142805.2:c.1176G>A

CA415086460

Gene: SLC6A8
Condition: creatine transporter deficiency
Inheritance Mode: X-linked inheritance
Link to MONDO
UUID: 620db564-09b2-4d12-8880-11763a9de93f
Approved on: 2024-03-28
Published on: 2024-03-28

HGVS expressions

NM_001142805.2:c.1176G>A
NC_000023.11:g.153693969G>A
CM000685.2:g.153693969G>A
NC_000023.10:g.152959424G>A
CM000685.1:g.152959424G>A
NC_000023.9:g.152612618G>A
NG_012016.1:g.10673G>A
NG_012016.2:g.10673G>A
ENST00000253122.10:c.1206G>A
ENST00000253122.9:c.1206G>A
ENST00000413787.1:c.258-235G>A
ENST00000430077.6:c.861G>A
ENST00000442457.1:c.260G>A
ENST00000457723.1:c.190G>A
ENST00000467402.1:n.305G>A
ENST00000485324.1:n.1239G>A
NM_001142805.1:c.1176G>A
NM_001142806.1:c.861G>A
NM_005629.3:c.1206G>A
NM_005629.4:c.1206G>A

Pathogenic

Met criteria codes 3
PM2_Supporting PP4 PVS1
Not Met criteria codes 1
PS3

Evidence Links 0

Expert Panel

Criteria Specification Information

Criteria Specifications for this VCEP
Evidence submitted by expert panel
Cerebral Creatine Deficiency Syndromes VCEP
The NM_005629.4:c.1206G>A variant in SLC6A8 is a nonsense variant predicted to cause a premature stop codon in biologically relevant exon 8/13 leading to nonsense mediated decay in a gene in which loss-of-function is an established disease mechanism (p.Trp402Ter). This variant was reported to result in reduced (<10% of wild-type) creatine transport activity in SLC6A8 deficient fibroblasts (PMID: 22281021) (PVS1). This variant has been reported in one hemizygous male individual with elevated urinary creatine/creatinine (PMID: 23644449) (PP4). The variant is absent in gnomAD v2.1.1. (PM2_Supporting). In summary, this variant meets criteria to be classified as pathogenic for creatine transporter deficiency. SLC6A8-specific criteria applied, as specified by the ClinGen CCDS VCEP (Specifications Version 1.1.0): PVS1, PM2_Supporting, PP4. (Classification approved by the ClinGen Cerebral Creatine Deficiency Syndromes Variant Curation Expert Panel on March 28, 2024).
Met criteria codes
PM2_Supporting
The variant is absent in gnomAD v2.1.1. (PM2_Supporting).
PP4
This variant has been reported in one hemizygous male individual with elevated urinary creatine/creatinine (PMID: 23644449) (PP4).
PVS1
The NM_005629.4:c.1206G>A variant in SLC6A8 is a nonsense variant predicted to cause a premature stop codon in biologically relevant exon 8/13 leading to nonsense mediated decay in a gene in which loss-of-function is an established disease mechanism (p.Trp402Ter). This variant was reported to result in reduced (<10% of wild-type) creatine transport activity in SLC6A8 deficient fibroblasts (PMID: 22281021) (PVS1).
Not Met criteria codes
PS3
This variant was reported to result in reduced (<10% of wild-type) creatine transport activity in SLC6A8 deficient fibroblasts (PMID: 22281021). Evidence noted under PVS1, per SVI guidance
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. If you have questions about the information contained on this website, please see a health care professional.
¤ Powered by BCM's Genboree.