rs2937639

Variant summary

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

The NM_001044.5(SLC6A3):​c.-45-371A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.498 in 152,170 control chromosomes in the GnomAD database, including 19,976 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 0.50 ( 19976 hom., cov: 33)

Consequence

SLC6A3
NM_001044.5 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.519

Publications

23 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=-0.86).
BA1
GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.589 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SLC6A3NM_001044.5 linkc.-45-371A>G intron_variant Intron 1 of 14 ENST00000270349.12 NP_001035.1 Q01959

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
SLC6A3ENST00000270349.12 linkc.-45-371A>G intron_variant Intron 1 of 14 1 NM_001044.5 ENSP00000270349.9 Q01959
SLC6A3ENST00000713696.1 linkc.-45-371A>G intron_variant Intron 1 of 14 ENSP00000519000.1
SLC6A3ENST00000713698.1 linkc.-45-371A>G intron_variant Intron 1 of 4 ENSP00000519002.1
SLC6A3ENST00000713697.1 linkn.-45-371A>G intron_variant Intron 1 of 10 ENSP00000519001.1

Frequencies

GnomAD3 genomes
AF:
0.498
AC:
75721
AN:
152050
Hom.:
19959
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.360
Gnomad AMI
AF:
0.635
Gnomad AMR
AF:
0.479
Gnomad ASJ
AF:
0.605
Gnomad EAS
AF:
0.174
Gnomad SAS
AF:
0.497
Gnomad FIN
AF:
0.558
Gnomad MID
AF:
0.564
Gnomad NFE
AF:
0.594
Gnomad OTH
AF:
0.518
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.498
AC:
75783
AN:
152170
Hom.:
19976
Cov.:
33
AF XY:
0.496
AC XY:
36913
AN XY:
74394
show subpopulations
African (AFR)
AF:
0.359
AC:
14914
AN:
41496
American (AMR)
AF:
0.480
AC:
7339
AN:
15302
Ashkenazi Jewish (ASJ)
AF:
0.605
AC:
2098
AN:
3470
East Asian (EAS)
AF:
0.174
AC:
904
AN:
5182
South Asian (SAS)
AF:
0.499
AC:
2408
AN:
4824
European-Finnish (FIN)
AF:
0.558
AC:
5907
AN:
10582
Middle Eastern (MID)
AF:
0.571
AC:
168
AN:
294
European-Non Finnish (NFE)
AF:
0.594
AC:
40367
AN:
67996
Other (OTH)
AF:
0.520
AC:
1100
AN:
2114
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.504
Heterozygous variant carriers
0
1888
3776
5664
7552
9440
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Genome Hom
Variant carriers
0
682
1364
2046
2728
3410
<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:
0.553
Hom.:
15836
Bravo
AF:
0.482
Asia WGS
AF:
0.356
AC:
1239
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.86
CADD
Benign
7.0
DANN
Benign
0.43
PhyloP100
-0.52
Mutation Taster
=100/0
polymorphism (auto)

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.14
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: rs2937639; hg19: chr5-1443728; API