chr5-1392596-G-A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001044.5(SLC6A3):​c.*2139C>T variant causes a downstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.207 in 151,614 control chromosomes in the GnomAD database, including 3,580 homozygotes. 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: 𝑓 0.21 ( 3580 hom., cov: 31)

Consequence

SLC6A3
NM_001044.5 downstream_gene

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -3.56

Publications

10 publications found
Variant links:
Genes affected
SLC6A3 (HGNC:11049): (solute carrier family 6 member 3) This gene encodes a dopamine transporter which is a member of the sodium- and chloride-dependent neurotransmitter transporter family. The 3' UTR of this gene contains a 40 bp tandem repeat, referred to as a variable number tandem repeat or VNTR, which can be present in 3 to 11 copies. Variation in the number of repeats is associated with idiopathic epilepsy, attention-deficit hyperactivity disorder, dependence on alcohol and cocaine, susceptibility to Parkinson disease and protection against nicotine dependence.[provided by RefSeq, Nov 2009]
SLC6A3 Gene-Disease associations (from GenCC):
  • classic dopamine transporter deficiency syndrome
    Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P
  • SLC6A3-related dopamine transporter deficiency syndrome
    Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
  • parkinsonism-dystonia, infantile
    Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.94).
BA1
GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.256 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SLC6A3NM_001044.5 linkc.*2139C>T downstream_gene_variant ENST00000270349.12 NP_001035.1 Q01959

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
SLC6A3ENST00000270349.12 linkc.*2139C>T downstream_gene_variant 1 NM_001044.5 ENSP00000270349.9 Q01959

Frequencies

GnomAD3 genomes
AF:
0.207
AC:
31422
AN:
151498
Hom.:
3581
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.130
Gnomad AMI
AF:
0.213
Gnomad AMR
AF:
0.205
Gnomad ASJ
AF:
0.399
Gnomad EAS
AF:
0.0671
Gnomad SAS
AF:
0.166
Gnomad FIN
AF:
0.186
Gnomad MID
AF:
0.383
Gnomad NFE
AF:
0.260
Gnomad OTH
AF:
0.249
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.207
AC:
31420
AN:
151614
Hom.:
3580
Cov.:
31
AF XY:
0.204
AC XY:
15079
AN XY:
74074
show subpopulations
African (AFR)
AF:
0.130
AC:
5398
AN:
41406
American (AMR)
AF:
0.205
AC:
3118
AN:
15244
Ashkenazi Jewish (ASJ)
AF:
0.399
AC:
1387
AN:
3472
East Asian (EAS)
AF:
0.0667
AC:
340
AN:
5098
South Asian (SAS)
AF:
0.165
AC:
788
AN:
4774
European-Finnish (FIN)
AF:
0.186
AC:
1956
AN:
10502
Middle Eastern (MID)
AF:
0.395
AC:
116
AN:
294
European-Non Finnish (NFE)
AF:
0.260
AC:
17608
AN:
67814
Other (OTH)
AF:
0.245
AC:
516
AN:
2102
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.500
Heterozygous variant carriers
0
1236
2472
3707
4943
6179
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Genome Hom
Variant carriers
0
326
652
978
1304
1630
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
Alfa
AF:
0.219
Hom.:
2376
Bravo
AF:
0.208
Asia WGS
AF:
0.110
AC:
382
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.94
CADD
Benign
0.27
DANN
Benign
0.56
PhyloP100
-3.6

Splicing

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

Publications

Other links and lift over

dbSNP: rs3863145; hg19: chr5-1392711; API