Variant: NM_005629.4(SLC6A8):c.116G>A (p.Gly39Asp)

CA16616458

410221 (ClinVar)

Gene: SLC6A8

Condition: creatine transporter deficiency

Inheritance Mode: X-linked inheritance

UUID: c417ca3f-9c6f-4b3b-84cc-991f7426a1d8

Approved on: 2022-06-06

Published on: 2022-10-08

HGVS expressions

NM_005629.4:c.116G>A
NM_005629.4(SLC6A8):c.116G>A (p.Gly39Asp)
NC_000023.11:g.153688690G>A
CM000685.2:g.153688690G>A
NC_000023.10:g.152954145G>A
CM000685.1:g.152954145G>A
NC_000023.9:g.152607339G>A
NG_012016.1:g.5394G>A
NG_012016.2:g.5394G>A
ENST00000253122.10:c.116G>A
ENST00000253122.9:c.116G>A
ENST00000458354.5:c.-3+125C>T
ENST00000480693.1:n.64+125C>T
NM_001142805.1:c.116G>A
NM_005629.3:c.116G>A
NM_001142805.2:c.116G>A

Uncertain Significance

• Met criteria codes: PM2 BP4

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

Evidence submitted by expert panel

Cerebral Creatine Deficiency Syndromes VCEP

The NM_005629.4(SLC6A8):c.116G>A (p.Gly39Asp) variant in SLC6A8 is a missense variant predicted to cause substitution of Glycine for Aspartic Acid at amino acid 39 (p.Gly39Asp). This variant is absent from gnomAD v2.1.1, therefore PM2_Supporting criteria is applicable. The computational predictor REVEL gives a score of 0.107 which is below the threshold of 0.25, and does not predict a damaging effect on SLC6A8 function, and SpliceAI predicts no impact on splicing (BP4). This variant has not been previously reported in affected individuals in the literature. There is a ClinVar entry for this variant (Variation ID:410221). In summary, this variant meets the criteria to be classified as a Variant of Uncertain Significance 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): PM2_Supporting, BP4. (Classification approved by the ClinGen CCDS VCEP on June 6, 2022).

Met criteria codes

• PM2: This variant is absent from gnomAD v2.1.1, therefore PM2_Supporting criteria is applicable.
• BP4: The computational predictor REVEL gives a score of 0.107 which is below the threshold of 0.25, and does not predict a damaging effect on SLC6A8 function, and SpliceAI predicts no impact on splicing (BP4).