NM_003042.4:c.1738C>T
Variant summary
Our verdict is Benign. Variant got -13 ACMG points: 1P and 14B. PP2BP4_ModerateBP6_Very_StrongBS2
The NM_003042.4(SLC6A1):c.1738C>T(p.Pro580Ser) 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 1,613,908 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P580A) has been classified as Uncertain significance.
Frequency
Consequence
NM_003042.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -13 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
SLC6A1 | NM_003042.4 | c.1738C>T | p.Pro580Ser | missense_variant | Exon 16 of 16 | ENST00000287766.10 | NP_003033.3 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000197 AC: 3AN: 152148Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000637 AC: 16AN: 251212Hom.: 0 AF XY: 0.0000663 AC XY: 9AN XY: 135774
GnomAD4 exome AF: 0.0000280 AC: 41AN: 1461760Hom.: 0 Cov.: 30 AF XY: 0.0000330 AC XY: 24AN XY: 727198
GnomAD4 genome AF: 0.0000197 AC: 3AN: 152148Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74304
ClinVar
Submissions by phenotype
Epilepsy with myoclonic atonic seizures Benign:1
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not specified Benign:1
Variant summary: SLC6A1 c.1738C>T (p.Pro580Ser) results in a non-conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 6.4e-05 in 251212 control chromosomes. c.1738C>T has been reported in the literature in individuals affected with Epilepsy without sufficient evidence for causality (Silva_2024). These report(s) do not provide unequivocal conclusions about association of the variant with Myoclonic-Atonic Epilepsy. At least one publication reports experimental evidence evaluating an impact on protein function. These results showed no damaging effect of this variant (Silva_2024). The following publication has been ascertained in the context of this evaluation (PMID: 38781976). ClinVar contains an entry for this variant (Variation ID: 568080). Based on the evidence outlined above, the variant was classified as likely benign. -
Inborn genetic diseases Benign:1
This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -
not provided Benign:1
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at