rs782244505
Variant summary
Our verdict is Likely pathogenic. Variant got 8 ACMG points: 8P and 0B. PM1PM2PP3_Strong
The NM_005629.4(SLC6A8):āc.1713C>Gā(p.Cys571Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000885 in 113,004 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ). Synonymous variant affecting the same amino acid position (i.e. C571C) has been classified as Likely benign.
Frequency
Consequence
NM_005629.4 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Likely_pathogenic. Variant got 8 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SLC6A8 | NM_005629.4 | c.1713C>G | p.Cys571Trp | missense_variant | 12/13 | ENST00000253122.10 | |
SLC6A8 | NM_001142805.2 | c.1683C>G | p.Cys561Trp | missense_variant | 12/13 | ||
SLC6A8 | NM_001142806.1 | c.1368C>G | p.Cys456Trp | missense_variant | 12/13 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SLC6A8 | ENST00000253122.10 | c.1713C>G | p.Cys571Trp | missense_variant | 12/13 | 1 | NM_005629.4 | P1 | |
SLC6A8 | ENST00000430077.6 | c.1368C>G | p.Cys456Trp | missense_variant | 12/13 | 2 | |||
SLC6A8 | ENST00000485324.1 | n.2020C>G | non_coding_transcript_exon_variant | 5/6 | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.00000885 AC: 1AN: 113004Hom.: 0 Cov.: 25 AF XY: 0.00 AC XY: 0AN XY: 35158
GnomAD4 exome Cov.: 37
GnomAD4 genome ? AF: 0.00000885 AC: 1AN: 113004Hom.: 0 Cov.: 25 AF XY: 0.00 AC XY: 0AN XY: 35158
ClinVar
Submissions by phenotype
Creatine transporter deficiency Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Nov 22, 2022 | In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt SLC6A8 protein function. ClinVar contains an entry for this variant (Variation ID: 1478075). This variant has not been reported in the literature in individuals affected with SLC6A8-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces cysteine, which is neutral and slightly polar, with tryptophan, which is neutral and slightly polar, at codon 571 of the SLC6A8 protein (p.Cys571Trp). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at