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: 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

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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC6A3	NM_001044.5 link	c.*972C>T		3_prime_UTR_variant	Exon 15 of 15	ENST00000270349.12	NP_001035.1	Q01959

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC6A3	ENST00000270349.12 link	c.*972C>T		3_prime_UTR_variant	Exon 15 of 15	1	NM_001044.5	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 v4.3

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over