chr3-11017239-G-A
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 3P and 2B. PM2PP2BP4_Moderate
The NM_003042.4(SLC6A1):c.28G>A(p.Asp10Asn) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000031 in 1,613,692 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★). Synonymous variant affecting the same amino acid position (i.e. D10D) has been classified as Benign.
Frequency
Consequence
NM_003042.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SLC6A1 | NM_003042.4 | c.28G>A | p.Asp10Asn | missense_variant | 3/16 | ENST00000287766.10 | |
SLC6A1-AS1 | NR_046647.1 | n.105+1881C>T | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SLC6A1 | ENST00000287766.10 | c.28G>A | p.Asp10Asn | missense_variant | 3/16 | 1 | NM_003042.4 | P1 | |
SLC6A1-AS1 | ENST00000414969.2 | n.105+1881C>T | intron_variant, non_coding_transcript_variant | 4 |
Frequencies
GnomAD3 genomes AF: 0.00000658 AC: 1AN: 151946Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00000797 AC: 2AN: 250926Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135766
GnomAD4 exome AF: 0.00000274 AC: 4AN: 1461746Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0AN XY: 727178
GnomAD4 genome AF: 0.00000658 AC: 1AN: 151946Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74196
ClinVar
Submissions by phenotype
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Nov 21, 2022 | The c.28G>A (p.D10N) alteration is located in exon 3 (coding exon 1) of the SLC6A1 gene. This alteration results from a G to A substitution at nucleotide position 28, causing the aspartic acid (D) at amino acid position 10 to be replaced by an asparagine (N). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Myoclonic-atonic epilepsy Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Apr 19, 2021 | 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 SLC6A1 protein function. This variant has not been reported in the literature in individuals with SLC6A1-related conditions. This variant is present in population databases (rs751108300, ExAC 0.003%). This sequence change replaces aspartic acid with asparagine at codon 10 of the SLC6A1 protein (p.Asp10Asn). The aspartic acid residue is moderately conserved and there is a small physicochemical difference between aspartic acid and asparagine. - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Apr 01, 2023 | SLC6A1: PP2 - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at