dbSNP rs6876890: SLC6A3:c.*972C>T (chr5-1393763-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_001044.5(SLC6A3):c.*972C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. 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 ( 3187 hom., cov: 19)

Exomes 𝑓: 0.19 ( 48 hom. )

Consequence

SLC6A3
NM_001044.5 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.94

Publications

12 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: PanelApp Australia, 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

SLC6A3 links:

Genome browser will be placed here

new If you want to explore the variant's impact on the transcript NM_001044.5, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

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=-1.0).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.223 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001044.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC6A3	NM_001044.5	MANE Select	c.*972C>T		3_prime_UTR	Exon 15 of 15	NP_001035.1	Q01959

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC6A3	ENST00000270349.12	TSL:1 MANE Select	c.*972C>T		3_prime_UTR	Exon 15 of 15	ENSP00000270349.9	Q01959

Frequencies

GnomAD3 genomes

AF:

0.207

AC:

25423

AN:

122792

Hom.:

3177

Cov.:

show subpopulations

Gnomad AFR

AF:

0.200

Gnomad AMI

AF:

0.157

Gnomad AMR

AF:

0.182

Gnomad ASJ

AF:

0.377

Gnomad EAS

AF:

0.0782

Gnomad SAS

AF:

0.185

Gnomad FIN

AF:

0.144

Gnomad MID

AF:

0.342

Gnomad NFE

AF:

0.227

Gnomad OTH

AF:

0.233

GnomAD4 exome

AF:

0.189

AC:

278

AN:

1468

Hom.:

Cov.:

AF XY:

0.179

AC XY:

158

AN XY:

882

show subpopulations

African (AFR)

AF:

0.313

AC:

AN:

American (AMR)

AF:

0.00

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

East Asian (EAS)

AF:

0.00

AC:

AN:

South Asian (SAS)

AF:

0.188

AC:

AN:

European-Finnish (FIN)

AF:

0.223

AC:

AN:

444

Middle Eastern (MID)

AF:

0.234

AC:

125

AN:

534

European-Non Finnish (NFE)

AF:

0.0659

AC:

AN:

334

Other (OTH)

AF:

0.211

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.472

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<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

AF:

0.207

AC:

25449

AN:

122868

Hom.:

3187

Cov.:

AF XY:

0.203

AC XY:

12009

AN XY:

59160

show subpopulations

African (AFR)

AF:

0.200

AC:

6211

AN:

31028

American (AMR)

AF:

0.182

AC:

2271

AN:

12486

Ashkenazi Jewish (ASJ)

AF:

0.377

AC:

1113

AN:

2950

East Asian (EAS)

AF:

0.0777

AC:

336

AN:

4326

South Asian (SAS)

AF:

0.184

AC:

660

AN:

3582

European-Finnish (FIN)

AF:

0.144

AC:

1124

AN:

7822

Middle Eastern (MID)

AF:

0.355

AC:

AN:

186

European-Non Finnish (NFE)

AF:

0.227

AC:

13176

AN:

58118

Other (OTH)

AF:

0.231

AC:

375

AN:

1624

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.484

Heterozygous variant carriers

825

1650

2475

3300

4125

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

236

472

708

944

1180

<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:

0.248

Hom.:

362

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-1.0

CADD

Benign

5.4

(source)

DANN

Benign

0.29

PhyloP100

-1.9

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over