rs143916832
Variant summary
Our verdict is Pathogenic. The variant received 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_005629.4(SLC6A8):c.1494C>G(p.Tyr498*) variant causes a stop gained, splice region change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. 2/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Pathogenic (★). Synonymous variant affecting the same amino acid position (i.e. Y498Y) has been classified as Likely benign. Variant results in nonsense mediated mRNA decay.
Frequency
Consequence
NM_005629.4 stop_gained, splice_region
Scores
Clinical Significance
Conservation
Publications
- creatine transporter deficiencyInheritance: XL Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: G2P, Orphanet, ClinGen, Labcorp Genetics (formerly Invitae)
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ACMG classification
Our verdict: Pathogenic. The variant received 12 ACMG points.
Variant Effect in Transcripts
ACMG analysis was done for transcript: NM_005629.4. You can select a different transcript below to see updated ACMG assignments.
RefSeq Transcripts
| Selected | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| SLC6A8 | NM_005629.4 | MANE Select | c.1494C>G | p.Tyr498* | stop_gained splice_region | Exon 10 of 13 | NP_005620.1 | ||
| SLC6A8 | NM_001142805.2 | c.1464C>G | p.Tyr488* | stop_gained splice_region | Exon 10 of 13 | NP_001136277.1 | |||
| SLC6A8 | NM_001142806.1 | c.1149C>G | p.Tyr383* | stop_gained splice_region | Exon 10 of 13 | NP_001136278.1 |
Ensembl Transcripts
| Selected | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| SLC6A8 | ENST00000253122.10 | TSL:1 MANE Select | c.1494C>G | p.Tyr498* | stop_gained splice_region | Exon 10 of 13 | ENSP00000253122.5 | ||
| SLC6A8 | ENST00000430077.6 | TSL:2 | c.1149C>G | p.Tyr383* | stop_gained splice_region | Exon 10 of 13 | ENSP00000403041.2 | ||
| SLC6A8 | ENST00000413787.1 | TSL:5 | c.423C>G | p.Tyr141* | stop_gained splice_region | Exon 5 of 6 | ENSP00000400463.1 |
Frequencies
GnomAD3 genomes Cov.: 23
GnomAD4 exome Cov.: 34
GnomAD4 genome Cov.: 23
ClinVar
ClinVar submissions as Germline
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at