GeneBe

3-11031206-C-T

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2BP4_StrongBP7

The NM_003042.4(SLC6A1):​c.1353C>T​(p.Asp451Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000686 in 1,458,642 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

SLC6A1
NM_003042.4 synonymous

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.129

Publications

0 publications found
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 Gene-Disease associations (from GenCC):
  • epilepsy with myoclonic atonic seizures
    Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Ambry Genetics, Illumina, G2P, Labcorp Genetics (formerly Invitae)
  • myoclonic-astatic epilepsy
    Inheritance: Unknown Classification: SUPPORTIVE Submitted by: Orphanet

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -3 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.47).
BP7
Synonymous conserved (PhyloP=-0.129 with no splicing effect.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SLC6A1NM_003042.4 linkc.1353C>T p.Asp451Asp synonymous_variant Exon 13 of 16 ENST00000287766.10 NP_003033.3 A0A024R2K8

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
SLC6A1ENST00000287766.10 linkc.1353C>T p.Asp451Asp synonymous_variant Exon 13 of 16 1 NM_003042.4 ENSP00000287766.4 P30531

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
6.86e-7
AC:
1
AN:
1458642
Hom.:
0
Cov.:
28
AF XY:
0.00
AC XY:
0
AN XY:
725910
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
33436
American (AMR)
AF:
0.00
AC:
0
AN:
44708
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
26110
East Asian (EAS)
AF:
0.00
AC:
0
AN:
39678
South Asian (SAS)
AF:
0.00
AC:
0
AN:
86178
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
53336
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
5758
European-Non Finnish (NFE)
AF:
9.02e-7
AC:
1
AN:
1109156
Other (OTH)
AF:
0.00
AC:
0
AN:
60282
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.475
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Variant carriers
0
2
4
6
8
10
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.47
CADD
Benign
3.9
DANN
Benign
0.45
PhyloP100
-0.13

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.020
Details are displayed if max score is > 0.2

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

Publications

Other links and lift over

dbSNP: rs1553691122; hg19: chr3-11072892; API