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GeneBe

rs759515813

Positions:

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 3P and 2B. PM2PP2BP6_Moderate

The NM_003042.4(SLC6A1):​c.1213A>C​(p.Ile405Leu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Benign (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. I405V) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 32)

Consequence

SLC6A1
NM_003042.4 missense

Scores

3
5
6

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 6.17
Variant links:
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 Uncertain_significance. Variant got 1 ACMG points.

PM2
?
    PM2 - Absent from controls (or at extremely low frequency if recessive) in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium
Very rare variant in population databases, with high coverage;
PP2
?
    PP2 - Missense variant in a gene that has a low rate of benign missense variation and in which missense variants are a common mechanism of disease
Missense variant where missense usually causes diseases, SLC6A1
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 3-11029242-A-C is Benign according to our data. Variant chr3-11029242-A-C is described in ClinVar as [Benign]. Clinvar id is 1167091.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
SLC6A1NM_003042.4 linkuse as main transcriptc.1213A>C p.Ile405Leu missense_variant 12/16 ENST00000287766.10

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
SLC6A1ENST00000287766.10 linkuse as main transcriptc.1213A>C p.Ile405Leu missense_variant 12/161 NM_003042.4 P1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
Cov.:
32
GnomAD4 exome
Cov.:
32
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
Cov.:
32

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

Myoclonic-atonic epilepsy Benign:1
Benign, criteria provided, single submitterclinical testingInvitaeOct 05, 2020- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.68
BayesDel_addAF
Uncertain
0.12
D
BayesDel_noAF
Uncertain
-0.060
CADD
Uncertain
24
DANN
Uncertain
0.99
DEOGEN2
Benign
0.25
T;T;T;T;T;.;T;.;T;T;T;T;.;T;T;T;.;T;T;T;.;T;T;T;.
Eigen
Benign
0.15
Eigen_PC
Uncertain
0.31
FATHMM_MKL
Pathogenic
0.99
D
M_CAP
Benign
0.055
D
MetaRNN
Uncertain
0.67
D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D
MetaSVM
Benign
-0.38
T
MutationAssessor
Benign
1.8
L;L;L;L;L;.;L;.;L;L;L;L;.;L;L;L;.;L;L;L;.;L;L;L;.
MutationTaster
Benign
1.0
D;D
PrimateAI
Pathogenic
0.83
D
Polyphen
0.031
B;B;B;B;B;.;B;.;B;B;B;B;.;B;B;B;.;B;B;B;.;B;B;B;.
Vest4
0.58
MutPred
0.62
Loss of catalytic residue at I405 (P = 0.1211);Loss of catalytic residue at I405 (P = 0.1211);Loss of catalytic residue at I405 (P = 0.1211);Loss of catalytic residue at I405 (P = 0.1211);Loss of catalytic residue at I405 (P = 0.1211);.;Loss of catalytic residue at I405 (P = 0.1211);.;Loss of catalytic residue at I405 (P = 0.1211);Loss of catalytic residue at I405 (P = 0.1211);Loss of catalytic residue at I405 (P = 0.1211);Loss of catalytic residue at I405 (P = 0.1211);.;Loss of catalytic residue at I405 (P = 0.1211);Loss of catalytic residue at I405 (P = 0.1211);Loss of catalytic residue at I405 (P = 0.1211);.;Loss of catalytic residue at I405 (P = 0.1211);Loss of catalytic residue at I405 (P = 0.1211);Loss of catalytic residue at I405 (P = 0.1211);.;Loss of catalytic residue at I405 (P = 0.1211);Loss of catalytic residue at I405 (P = 0.1211);Loss of catalytic residue at I405 (P = 0.1211);.;
MVP
0.74
MPC
1.2
ClinPred
0.90
D
GERP RS
5.6
Varity_R
0.55
gMVP
0.89

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.090
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr3-11070928; API