chr3-11017216-C-T

Variant summary

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

The NM_003042.4(SLC6A1):​c.5C>T​(p.Ala2Val) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,250 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. A2E) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

SLC6A1
NM_003042.4 missense

Scores

1
10
8

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 5.52
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]
SLC6A1-AS1 (HGNC:40546): (SLC6A1 antisense RNA 1)

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP2
Missense variant in gene, where missense usually causes diseases (based on misZ statistic), SLC6A1. . Gene score misZ 4.1766 (greater than the threshold 3.09). Trascript score misZ 4.9229 (greater than threshold 3.09). GenCC has associacion of gene with myoclonic-atonic epilepsy, myoclonic-astatic epilepsy.
BP6
Variant 3-11017216-C-T is Benign according to our data. Variant chr3-11017216-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2155429.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.5C>T p.Ala2Val missense_variant 3/16 ENST00000287766.10
SLC6A1-AS1NR_046647.1 linkuse as main transcriptn.105+1904G>A intron_variant, non_coding_transcript_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
SLC6A1ENST00000287766.10 linkuse as main transcriptc.5C>T p.Ala2Val missense_variant 3/161 NM_003042.4 P1
SLC6A1-AS1ENST00000414969.2 linkuse as main transcriptn.105+1904G>A intron_variant, non_coding_transcript_variant 4

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
6.84e-7
AC:
1
AN:
1461250
Hom.:
0
Cov.:
31
AF XY:
0.00
AC XY:
0
AN XY:
726844
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000252
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32
Bravo
AF:
0.00000756

ClinVar

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

Submissions by phenotype

Myoclonic-atonic epilepsy Benign:1
Likely benign, criteria provided, single submitterclinical testingInvitaeAug 16, 2022- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
0.37
BayesDel_addAF
Uncertain
0.070
D
BayesDel_noAF
Benign
-0.14
CADD
Pathogenic
28
DANN
Pathogenic
1.0
DEOGEN2
Benign
0.27
T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;.;T;.;T;T;.;.;.
Eigen
Uncertain
0.31
Eigen_PC
Uncertain
0.37
FATHMM_MKL
Uncertain
0.95
D
LIST_S2
Benign
0.25
.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;T;.;.;.;T;T;T;T
M_CAP
Benign
0.038
D
MetaRNN
Uncertain
0.47
T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T
MetaSVM
Benign
-0.42
T
MutationAssessor
Benign
0.97
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
Uncertain
0.71
T
PROVEAN
Benign
-0.70
.;N;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.
REVEL
Uncertain
0.29
Sift
Uncertain
0.0090
.;D;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.
Sift4G
Uncertain
0.013
.;D;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.
Polyphen
0.99
D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;.;D;.;D;D;.;.;.
Vest4
0.63
MutPred
0.20
Gain of MoRF binding (P = 0.0994);Gain of MoRF binding (P = 0.0994);Gain of MoRF binding (P = 0.0994);Gain of MoRF binding (P = 0.0994);Gain of MoRF binding (P = 0.0994);Gain of MoRF binding (P = 0.0994);Gain of MoRF binding (P = 0.0994);Gain of MoRF binding (P = 0.0994);Gain of MoRF binding (P = 0.0994);Gain of MoRF binding (P = 0.0994);Gain of MoRF binding (P = 0.0994);Gain of MoRF binding (P = 0.0994);Gain of MoRF binding (P = 0.0994);Gain of MoRF binding (P = 0.0994);Gain of MoRF binding (P = 0.0994);Gain of MoRF binding (P = 0.0994);Gain of MoRF binding (P = 0.0994);Gain of MoRF binding (P = 0.0994);Gain of MoRF binding (P = 0.0994);Gain of MoRF binding (P = 0.0994);Gain of MoRF binding (P = 0.0994);Gain of MoRF binding (P = 0.0994);Gain of MoRF binding (P = 0.0994);Gain of MoRF binding (P = 0.0994);
MVP
0.67
MPC
1.8
ClinPred
0.92
D
GERP RS
4.4
Varity_R
0.10
gMVP
0.66

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs913073947; hg19: chr3-11058902; API