rs782028471
Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2
The NM_005629.4(SLC6A8):c.1627G>A(p.Glu543Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000273 in 1,209,700 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 12 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. E543Q) has been classified as Benign.
Frequency
Consequence
NM_005629.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -6 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SLC6A8 | NM_005629.4 | c.1627G>A | p.Glu543Lys | missense_variant | 12/13 | ENST00000253122.10 | |
SLC6A8 | NM_001142805.2 | c.1597G>A | p.Glu533Lys | missense_variant | 12/13 | ||
SLC6A8 | NM_001142806.1 | c.1282G>A | p.Glu428Lys | missense_variant | 12/13 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SLC6A8 | ENST00000253122.10 | c.1627G>A | p.Glu543Lys | missense_variant | 12/13 | 1 | NM_005629.4 | P1 | |
SLC6A8 | ENST00000430077.6 | c.1282G>A | p.Glu428Lys | missense_variant | 12/13 | 2 | |||
SLC6A8 | ENST00000485324.1 | n.1934G>A | non_coding_transcript_exon_variant | 5/6 | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.0000178 AC: 2AN: 112486Hom.: 0 Cov.: 25 AF XY: 0.0000288 AC XY: 1AN XY: 34678
GnomAD3 exomes AF: 0.0000110 AC: 2AN: 182609Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 67637
GnomAD4 exome AF: 0.0000283 AC: 31AN: 1097214Hom.: 0 Cov.: 38 AF XY: 0.0000303 AC XY: 11AN XY: 362958
GnomAD4 genome ? AF: 0.0000178 AC: 2AN: 112486Hom.: 0 Cov.: 25 AF XY: 0.0000288 AC XY: 1AN XY: 34678
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Apr 23, 2015 | - - |
Creatine transporter deficiency Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jul 19, 2022 | This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 543 of the SLC6A8 protein (p.Glu543Lys). This variant is present in population databases (rs782028471, gnomAD 0.008%). This variant has not been reported in the literature in individuals affected with SLC6A8-related conditions. ClinVar contains an entry for this variant (Variation ID: 212212). 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. 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. - |
Creatine deficiency syndrome 1 Uncertain:1
Uncertain significance, no assertion criteria provided | clinical testing | Natera, Inc. | Nov 11, 2019 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at