rs1064795852
Variant summary
Our verdict is Pathogenic. Variant got 21 ACMG points: 21P and 0B. PS1PM1PM2PM5PP2PP3_ModeratePP5_Very_Strong
The NM_003042.4(SLC6A1):c.223G>A(p.Gly75Arg) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Likely pathogenic (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely pathogenicin ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G75E) has been classified as Likely pathogenic.
Frequency
Consequence
NM_003042.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 21 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SLC6A1 | NM_003042.4 | c.223G>A | p.Gly75Arg | missense_variant | 3/16 | ENST00000287766.10 | |
SLC6A1-AS1 | NR_046647.1 | n.105+1686C>T | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SLC6A1 | ENST00000287766.10 | c.223G>A | p.Gly75Arg | missense_variant | 3/16 | 1 | NM_003042.4 | P1 | |
SLC6A1-AS1 | ENST00000414969.2 | n.105+1686C>T | intron_variant, non_coding_transcript_variant | 4 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD4 exome Cov.: 31
GnomAD4 genome ? Cov.: 32
ClinVar
Submissions by phenotype
Myoclonic-atonic epilepsy Pathogenic:1Other:1
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Aug 04, 2023 | 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 SLC6A1 protein function. For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 422549). This missense change has been observed in individual(s) with clinical features of myoclonic-atonic epilepsy (PMID: 28708303, 29315614; Invitae). In at least one individual the variant was observed to be de novo. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces glycine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 75 of the SLC6A1 protein (p.Gly75Arg). - |
not provided, no classification provided | phenotyping only | GenomeConnect - Brain Gene Registry | - | Variant classified as Pathogenic and reported on 01-27-2020 by GeneDx. Assertions are reported exactly as they appear on the patient provided laboratory report. GenomeConnect does not attempt to reinterpret the variant. The IDDRC-CTSA National Brain Gene Registry (BGR) is a study funded by the U.S. National Center for Advancing Translational Sciences (NCATS) and includes 13 Intellectual and Developmental Disability Research Center (IDDRC) institutions. The study is led by Principal Investigator Dr. Philip Payne from Washington University. The BGR is a data commons of gene variants paired with subject clinical information. This database helps scientists learn more about genetic changes and their impact on the brain and behavior. Participation in the Brain Gene Registry requires participation in GenomeConnect. More information about the Brain Gene Registry can be found on the study website - https://braingeneregistry.wustl.edu/. - |
not provided Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | GeneDx | Jan 07, 2020 | Not observed in large population cohorts (Lek et al., 2016); In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 28708303, 29315614) - |
Myoclonic-astatic epilepsy Pathogenic:1
Likely pathogenic, criteria provided, single submitter | clinical testing | Groupe Hospitalier Pitie Salpetriere, UF Genomique du Developpement, Assistance Publique Hopitaux de Paris | Jan 06, 2017 | Intellectual disability, mild; epilepsy (absence seizures); weight stagnation; hypereosinophilia ; no myoclonic-atonic epilepsy - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at