5-1432710-G-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001044.5(SLC6A3):c.419-12C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.251 in 1,605,626 control chromosomes in the GnomAD database, including 57,552 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.31 ( 8283 hom., cov: 32)

Exomes 𝑓: 0.25 ( 49269 hom. )

Consequence

SLC6A3
NM_001044.5 intron

Scores

Splicing: ADA: 0.00003653

Clinical Significance

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

Conservation

PhyloP100: 0.662

Publications

43 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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BP6

Variant 5-1432710-G-T is Benign according to our data. Variant chr5-1432710-G-T is described in CliVar as Benign. Clinvar id is 522347.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-1432710-G-T is described in CliVar as Benign. Clinvar id is 522347.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-1432710-G-T is described in CliVar as Benign. Clinvar id is 522347.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-1432710-G-T is described in CliVar as Benign. Clinvar id is 522347.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-1432710-G-T is described in CliVar as Benign. Clinvar id is 522347.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-1432710-G-T is described in CliVar as Benign. Clinvar id is 522347.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.508 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC6A3	NM_001044.5 link	c.419-12C>A		intron_variant	Intron 3 of 14	ENST00000270349.12	NP_001035.1	Q01959

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
SLC6A3	ENST00000270349.12 link	c.419-12C>A	intron_variant	Intron 3 of 14	1	NM_001044.5	ENSP00000270349.9	Q01959
SLC6A3	ENST00000713696.1 link	c.419-12C>A	intron_variant	Intron 3 of 14			ENSP00000519000.1
SLC6A3	ENST00000713698.1 link	c.419-12C>A	intron_variant	Intron 3 of 4			ENSP00000519002.1
SLC6A3	ENST00000713697.1 link	n.419-12C>A	intron_variant	Intron 3 of 10			ENSP00000519001.1

Frequencies

GnomAD3 genomes

AF:

0.311

AC:

47180

AN:

151876

Hom.:

8274

Cov.:

show subpopulations

Gnomad AFR

AF:

0.440

Gnomad AMI

AF:

0.204

Gnomad AMR

AF:

0.334

Gnomad ASJ

AF:

0.281

Gnomad EAS

AF:

0.525

Gnomad SAS

AF:

0.416

Gnomad FIN

AF:

0.294

Gnomad MID

AF:

0.282

Gnomad NFE

AF:

0.210

Gnomad OTH

AF:

0.282

GnomAD2 exomes

AF:

0.305

AC:

75405

AN:

246960

AF XY:

0.304

show subpopulations

Gnomad AFR exome

AF:

0.449

Gnomad AMR exome

AF:

0.359

Gnomad ASJ exome

AF:

0.277

Gnomad EAS exome

AF:

0.516

Gnomad FIN exome

AF:

0.291

Gnomad NFE exome

AF:

0.210

Gnomad OTH exome

AF:

0.255

GnomAD4 exome

AF:

0.245

AC:

356468

AN:

1453632

Hom.:

49269

Cov.:

AF XY:

0.250

AC XY:

180725

AN XY:

723554

show subpopulations

African (AFR)

AF:

0.449

AC:

14956

AN:

33312

American (AMR)

AF:

0.352

AC:

15620

AN:

44378

Ashkenazi Jewish (ASJ)

AF:

0.277

AC:

7226

AN:

26090

East Asian (EAS)

AF:

0.529

AC:

20956

AN:

39588

South Asian (SAS)

AF:

0.420

AC:

36162

AN:

86056

European-Finnish (FIN)

AF:

0.285

AC:

15187

AN:

53232

Middle Eastern (MID)

AF:

0.264

AC:

1518

AN:

5746

European-Non Finnish (NFE)

AF:

0.207

AC:

228694

AN:

1105062

Other (OTH)

AF:

0.268

AC:

16149

AN:

60168

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

14063

28126

42190

56253

70316

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

8356

16712

25068

33424

41780

<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:

0.311

AC:

47229

AN:

151994

Hom.:

8283

Cov.:

AF XY:

0.318

AC XY:

23605

AN XY:

74266

show subpopulations

African (AFR)

AF:

0.440

AC:

18240

AN:

41448

American (AMR)

AF:

0.334

AC:

5102

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.281

AC:

975

AN:

3466

East Asian (EAS)

AF:

0.525

AC:

2694

AN:

5132

South Asian (SAS)

AF:

0.415

AC:

1997

AN:

4808

European-Finnish (FIN)

AF:

0.294

AC:

3104

AN:

10574

Middle Eastern (MID)

AF:

0.269

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.210

AC:

14254

AN:

67964

Other (OTH)

AF:

0.283

AC:

598

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1564

3128

4691

6255

7819

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

470

940

1410

1880

2350

<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:

0.240

Hom.:

20943

Bravo

AF:

0.317

Asia WGS

AF:

0.445

AC:

1546

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Classic dopamine transporter deficiency syndrome

Benign:2

Sep 21, 2015

Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Apr 19, 2015

Genome Diagnostics Laboratory, Amsterdam University Medical Center

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Jul 05, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Parkinsonism-dystonia, infantile

Benign:1

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

7.1

(source)

DANN

Benign

0.36

PhyloP100

0.66

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000037

dbscSNV1_RF

Benign

0.012

SpliceAI score (max)

0.040

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

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over