3-11017119-G-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_003042.4(SLC6A1):​c.-93G>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000012 in 835,032 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: 0.0000012 ( 0 hom. )

Consequence

SLC6A1
NM_003042.4 5_prime_UTR_premature_start_codon_gain

Scores

2
Splicing: ADA: 0.0002243
2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.91

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-AS1 (HGNC:40546): (SLC6A1 antisense RNA 1)

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.62).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SLC6A1NM_003042.4 linkc.-93G>T 5_prime_UTR_premature_start_codon_gain_variant Exon 3 of 16 ENST00000287766.10 NP_003033.3 A0A024R2K8
SLC6A1NM_003042.4 linkc.-93G>T 5_prime_UTR_variant Exon 3 of 16 ENST00000287766.10 NP_003033.3 A0A024R2K8

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
SLC6A1ENST00000287766.10 linkc.-93G>T 5_prime_UTR_premature_start_codon_gain_variant Exon 3 of 16 1 NM_003042.4 ENSP00000287766.4 P30531
SLC6A1ENST00000287766.10 linkc.-93G>T 5_prime_UTR_variant Exon 3 of 16 1 NM_003042.4 ENSP00000287766.4 P30531

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
0.00000120
AC:
1
AN:
835032
Hom.:
0
Cov.:
11
AF XY:
0.00000232
AC XY:
1
AN XY:
431056
show subpopulations
⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.
African (AFR)
AF:
0.00
AC:
0
AN:
21546
American (AMR)
AF:
0.00
AC:
0
AN:
38948
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
19042
East Asian (EAS)
AF:
0.00
AC:
0
AN:
35300
South Asian (SAS)
AF:
0.0000158
AC:
1
AN:
63210
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
47452
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
3044
European-Non Finnish (NFE)
AF:
0.00
AC:
0
AN:
567234
Other (OTH)
AF:
0.00
AC:
0
AN:
39256
⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.275
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.62
CADD
Benign
17
DANN
Benign
0.91
PhyloP100
1.9
PromoterAI
-0.017
Neutral

Splicing

Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Benign
0.00022
dbscSNV1_RF
Benign
0.0080
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

Other links and lift over

dbSNP: rs1024083730; hg19: chr3-11058805; COSMIC: COSV107288673; COSMIC: COSV107288673; API