rs33948309

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_003042.4(SLC6A1):​c.780G>A​(p.Thr260=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0035 in 1,614,052 control chromosomes in the GnomAD database, including 155 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.019 ( 98 hom., cov: 32)
Exomes 𝑓: 0.0019 ( 57 hom. )

Consequence

SLC6A1
NM_003042.4 synonymous

Scores

2

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -0.995
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.67).
BP6
Variant 3-11025514-G-A is Benign according to our data. Variant chr3-11025514-G-A is described in ClinVar as [Benign]. Clinvar id is 475490.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=-0.995 with no splicing effect.
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0634 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
SLC6A1NM_003042.4 linkuse as main transcriptc.780G>A p.Thr260= synonymous_variant 8/16 ENST00000287766.10 NP_003033.3

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
SLC6A1ENST00000287766.10 linkuse as main transcriptc.780G>A p.Thr260= synonymous_variant 8/161 NM_003042.4 ENSP00000287766 P1

Frequencies

GnomAD3 genomes
AF:
0.0189
AC:
2877
AN:
152106
Hom.:
98
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0655
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00733
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000208
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00633
Gnomad NFE
AF:
0.000294
Gnomad OTH
AF:
0.0138
GnomAD3 exomes
AF:
0.00481
AC:
1208
AN:
251360
Hom.:
30
AF XY:
0.00343
AC XY:
466
AN XY:
135842
show subpopulations
Gnomad AFR exome
AF:
0.0618
Gnomad AMR exome
AF:
0.00437
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.000131
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000264
Gnomad OTH exome
AF:
0.00293
GnomAD4 exome
AF:
0.00190
AC:
2773
AN:
1461828
Hom.:
57
Cov.:
31
AF XY:
0.00165
AC XY:
1198
AN XY:
727218
show subpopulations
Gnomad4 AFR exome
AF:
0.0617
Gnomad4 AMR exome
AF:
0.00494
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000252
Gnomad4 SAS exome
AF:
0.000151
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.000160
Gnomad4 OTH exome
AF:
0.00470
GnomAD4 genome
AF:
0.0189
AC:
2880
AN:
152224
Hom.:
98
Cov.:
32
AF XY:
0.0182
AC XY:
1351
AN XY:
74428
show subpopulations
Gnomad4 AFR
AF:
0.0654
Gnomad4 AMR
AF:
0.00725
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000208
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000294
Gnomad4 OTH
AF:
0.0137
Alfa
AF:
0.0113
Hom.:
32
Bravo
AF:
0.0218
Asia WGS
AF:
0.00289
AC:
10
AN:
3478
EpiCase
AF:
0.000491
EpiControl
AF:
0.000593

ClinVar

Significance: Benign
Submissions summary: Benign:5
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not provided Benign:3
Benign, criteria provided, single submitterclinical testingGeneDxJul 17, 2018- -
Benign, criteria provided, single submitternot providedBreakthrough Genomics, Breakthrough Genomics-- -
Benign, criteria provided, single submitterclinical testingAthena DiagnosticsSep 07, 2017- -
Inborn genetic diseases Benign:1
Benign, criteria provided, single submitterclinical testingAmbry GeneticsMar 17, 2016This 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 submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpFeb 01, 2024- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.67
CADD
Benign
6.7
DANN
Benign
0.70

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: rs33948309; hg19: chr3-11067200; API