Variant: NM_001142805.2:c.1288dup

CA2582121298

Gene: SLC6A8

Condition: creatine transporter deficiency

Inheritance Mode: X-linked inheritance

UUID: a9fc696c-f7a4-4aa0-a39a-b593baccbffa

HGVS expressions

NM_001142805.2:c.1288dup
NC_000023.11:g.153694193dup
CM000685.2:g.153694193dup
NC_000023.10:g.152959648dup
CM000685.1:g.152959648dup
NC_000023.9:g.152612842dup
NG_012016.1:g.10897dup
NG_012016.2:g.10897dup
ENST00000253122.10:c.1318dup
ENST00000253122.9:c.1318dup
ENST00000413787.1:c.258-11dup
ENST00000430077.6:c.973dup
ENST00000442457.1:c.372dup
ENST00000485324.1:n.1463dup
NM_001142805.1:c.1288dup
NM_001142806.1:c.973dup
NM_005629.3:c.1318dup
NM_005629.4:c.1318dup

Pathogenic

• Met criteria codes: PM2_Supporting PVS1 PP4

Expert Panel

Cerebral Creatine Deficiency Syndromes VCEP

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

Evidence submitted by expert panel

Cerebral Creatine Deficiency Syndromes VCEP

The NM_005629.4:c.1318dup variant in SLC6A8 is frameshift variant predicted to cause a premature stop codon in biologically relevant exon 9/13 leading to nonsense mediated decay in a gene in which loss of function is an established disease mechanism (p.Arg440ProfsTer25) (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 CCDS VCEP on March 25, 2024).

Met criteria codes

• PM2_Supporting: The variant is absent in gnomAD v2.1.1. (PM2_Supporting).
• PVS1: The NM_005629.4:c.1318dup variant in SLC6A8 is frameshift variant predicted to cause a premature stop codon in biologically relevant exon 9/13 leading to nonsense mediated decay in a gene in which loss of function is an established disease mechanism (p.Arg440ProfsTer25) (PVS1).
• PP4: This variant has been reported in one hemizygous male individual with elevated urinary creatine/creatinine (PMID: 23644449) (PP4).

Approved on: 2024-03-25

Published on: 2024-03-25