rs35972647
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Variant summary
Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BS1BS2
The NM_003042.4(SLC6A1):c.960C>T(p.Ser320=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00136 in 1,613,798 control chromosomes in the GnomAD database, including 29 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.0066 ( 14 hom., cov: 32)
Exomes 𝑓: 0.00081 ( 15 hom. )
Consequence
SLC6A1
NM_003042.4 synonymous
NM_003042.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.855
Genes affected
SLC6A1 (HGNC:11042): (solute carrier family 6 member 1) The protein encoded by this gene is a gamma-aminobutyric acid (GABA) transporter that localizes to the plasma membrane. The encoded protein removes GABA from the synaptic cleft, restoring it to presynaptic terminals. [provided by RefSeq, Jan 2017]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -19 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.25).
BP6
Variant 3-11026241-C-T is Benign according to our data. Variant chr3-11026241-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 475493.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=0.855 with no splicing effect.
BS1
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00661 (1006/152180) while in subpopulation AFR AF= 0.0225 (936/41514). AF 95% confidence interval is 0.0213. There are 14 homozygotes in gnomad4. There are 472 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
High AC in GnomAd4 at 1006 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SLC6A1 | NM_003042.4 | c.960C>T | p.Ser320= | synonymous_variant | 10/16 | ENST00000287766.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SLC6A1 | ENST00000287766.10 | c.960C>T | p.Ser320= | synonymous_variant | 10/16 | 1 | NM_003042.4 | P1 |
Frequencies
GnomAD3 genomes AF: 0.00658 AC: 1001AN: 152062Hom.: 13 Cov.: 32
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GnomAD3 exomes AF: 0.00184 AC: 461AN: 251114Hom.: 6 AF XY: 0.00137 AC XY: 186AN XY: 135710
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GnomAD4 exome AF: 0.000814 AC: 1190AN: 1461618Hom.: 15 Cov.: 33 AF XY: 0.000725 AC XY: 527AN XY: 727100
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GnomAD4 genome AF: 0.00661 AC: 1006AN: 152180Hom.: 14 Cov.: 32 AF XY: 0.00634 AC XY: 472AN XY: 74398
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:6
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:2
Benign, criteria provided, single submitter | clinical testing | GeneDx | Aug 30, 2019 | - - |
Benign, criteria provided, single submitter | clinical testing | Athena Diagnostics | May 31, 2018 | - - |
SLC6A1-related disorder Benign:1
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Jun 14, 2019 | This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Inborn genetic diseases Benign:1
Benign, criteria provided, single submitter | clinical testing | Ambry Genetics | May 14, 2016 | This alteration is classified as 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. - |
Myoclonic-atonic epilepsy Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 30, 2024 | - - |
Myoclonic-astatic epilepsy Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Oct 14, 2021 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at