rs1060502808
Variant summary
Our verdict is Pathogenic. Variant got 16 ACMG points: 16P and 0B. PVS1PP5_Very_Strong
The NM_005629.4(SLC6A8):c.974_975del(p.Thr325SerfsTer139) variant causes a frameshift change. Variant has been reported in ClinVar as Pathogenic (★★). Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: not found (cov: 24)
Consequence
SLC6A8
NM_005629.4 frameshift
NM_005629.4 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 5.98
Genes affected
SLC6A8 (HGNC:11055): (solute carrier family 6 member 8) The protein encoded by this gene is a plasma membrane protein whose function is to transport creatine into and out of cells. Defects in this gene can result in X-linked creatine deficiency syndrome. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Dec 2008]
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ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 16 ACMG points.
PVS1
?
Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
PP5
?
Variant X-153693321-TCA-T is Pathogenic according to our data. Variant chrX-153693321-TCA-T is described in ClinVar as [Pathogenic]. Clinvar id is 410218.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chrX-153693321-TCA-T is described in Lovd as [Pathogenic].
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SLC6A8 | NM_005629.4 | c.974_975del | p.Thr325SerfsTer139 | frameshift_variant | 6/13 | ENST00000253122.10 | |
SLC6A8 | NM_001142805.2 | c.974_975del | p.Thr325SerfsTer129 | frameshift_variant | 6/13 | ||
SLC6A8 | NM_001142806.1 | c.629_630del | p.Thr210SerfsTer139 | frameshift_variant | 6/13 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SLC6A8 | ENST00000253122.10 | c.974_975del | p.Thr325SerfsTer139 | frameshift_variant | 6/13 | 1 | NM_005629.4 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 24
GnomAD3 genomes
?
Cov.:
24
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome ? Cov.: 24
GnomAD4 genome
?
Cov.:
24
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Creatine transporter deficiency Pathogenic:2
Pathogenic, criteria provided, single submitter | clinical testing | Institute of Human Genetics Munich, Klinikum Rechts Der Isar, TU München | Oct 04, 2019 | - - |
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Apr 18, 2022 | This sequence change creates a premature translational stop signal (p.Thr325Serfs*139) in the SLC6A8 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in SLC6A8 are known to be pathogenic (PMID: 22281021). This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with X-linked cerebral creatine deficiency (PMID: 20602486). ClinVar contains an entry for this variant (Variation ID: 410218). For these reasons, this variant has been classified as Pathogenic. - |
Computational scores
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Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at