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Variant: NM_005629.4(SLC6A8):c.912+9G>A

CA10549344

383888 (ClinVar)

Gene: SLC6A8
Condition: creatine transporter deficiency
Inheritance Mode: X-linked inheritance
UUID: 4a0b1d92-d788-453f-ae58-7c2db7ad90ba
Approved on: 2022-06-06
Published on: 2022-10-08

HGVS expressions

NM_005629.4:c.912+9G>A
NM_005629.4(SLC6A8):c.912+9G>A
NC_000023.11:g.153693184G>A
CM000685.2:g.153693184G>A
NC_000023.10:g.152958639G>A
CM000685.1:g.152958639G>A
NC_000023.9:g.152611833G>A
NG_012016.1:g.9888G>A
NG_012016.2:g.9888G>A
ENST00000253122.10:c.912+9G>A
ENST00000253122.9:c.912+9G>A
ENST00000413787.1:n.122+9G>A
ENST00000430077.6:c.567+9G>A
ENST00000467402.1:n.146-308G>A
ENST00000485324.1:n.945+9G>A
NM_001142805.1:c.912+9G>A
NM_001142806.1:c.567+9G>A
NM_005629.3:c.912+9G>A
NM_001142805.2:c.912+9G>A
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Benign

Met criteria codes 2
BS2 BS1
Not Met criteria codes 1
BP4

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

Criteria Specification Approval History
Criteria Specifications for this VCEP
Evidence submitted by expert panel
Cerebral Creatine Deficiency Syndromes VCEP
The NM_005629.4:c.912+9G>A variant in SLC6A8 is in the region of the donor splice site of intron 5. The highest population minor allele frequency in gnomAD v2.1.1 is 0.004083 in the Latino/Admixed American population, meeting the ClinGen CCDS VCEP allele frequency threshold for BS1 (>0.0002) (BS1). The variant is present in 25 hemizygotes and 2 homozygotes in gnomAD v2.1.1 (BS2). The computational predictor, SpliceAI, predicts that the variant has no impact on splicing, and varSEAK indicates an unknown effect on splicing due to possible strengthening of a cryptic splice site in intron 5. To our knowledge, this variant has not been reported in any patients with features of creatine transporter deficiency the literature and no results of functional or splicing assays are unavailable. There is a ClinVar entry for this variant (Variation ID: 383888). In summary, this variant meets the criteria to be classified as benign for creatine transporter deficiency. SLC6A8-specific ACMG-AMP criteria applied, as specified by the ClinGen CCDS VCEP (Specifications Version 1.1.0): BS1, BS2. (Classification approved by the ClinGen CCDS VCEP on June 6, 2022).
Met criteria codes
BS2
The variant is present in 25 hemizygotes and 2 homozygotes in gnomAD v2.1.1 (BS2).
BS1
The highest population minor allele frequency in gnomAD v2.1.1 is 0.004083 in the Latino/Admixed American population. This is higher than the ClinGen CCDS VCEP's allele frequency threshold for BS1 (>0.0002), meeting this criterion (BS1).
Not Met criteria codes
BP4
The computational predictor, SpliceAI, predicts that the variant has no impact on splicing, but varSEAK indicates an unknown effect on splicing due to strengthening of a cryptic splice site (GT dinucleotide at +6, +7).
Curation History
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