Evidence Repository - Clinical Genome Resources

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_005629.4(SLC6A8):c.145G>C (p.Val49Leu)

CA415076485

658337 (ClinVar)

Gene: SLC6A8

Condition: creatine transporter deficiency

Inheritance Mode: X-linked inheritance

Link to MONDO

UUID: 80ccbd63-4032-4485-935e-dac7798a8cbf

Approved on: 2022-06-06

Published on: 2022-10-08

HGVS expressions

NM_005629.4:c.145G>C

NM_005629.4(SLC6A8):c.145G>C (p.Val49Leu)

NC_000023.11:g.153688719G>C

CM000685.2:g.153688719G>C

NC_000023.10:g.152954174G>C

CM000685.1:g.152954174G>C

NC_000023.9:g.152607368G>C

NG_012016.1:g.5423G>C

NG_012016.2:g.5423G>C

ENST00000253122.10:c.145G>C

ENST00000253122.9:c.145G>C

ENST00000458354.5:c.-3+96C>G

ENST00000480693.1:n.64+96C>G

NM_001142805.1:c.145G>C

NM_005629.3:c.145G>C

NM_001142805.2:c.145G>C

Uncertain Significance

PM2 BP4

Evidence Links 0

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

Criteria Specification Approval History

Criteria Specifications for this VCEP

Evidence submitted by expert panel

Cerebral Creatine Deficiency Syndromes VCEP

The NM_005629.4(SLC6A8):c.145G>C (p.Val49Leu) variant in SLC6A8 is a missense variant predicted to cause substitution of Valine for Leucine at amino acid 49 (p.Val49Leu). This variant is absent from gnomAD v2.1.1, therefore PM2_Supporting criteria is applicable. The computational predictor REVEL gives a score of 0.032 which is below the threshold of 0.25, and does not predict a damaging effect on SLC6A8 function, and SpliceAI does no predict an 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:658337). 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).

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 0.032 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).

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