5-1411297-T-C

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001044.5(SLC6A3):c.1215A>G(p.Ser405Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.267 in 1,554,866 control chromosomes in the GnomAD database, including 59,254 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.32 ( 8750 hom., cov: 33)

Exomes 𝑓: 0.26 ( 50504 hom. )

Consequence

SLC6A3
NM_001044.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: -6.82

Publications

88 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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.96).

BP6

Variant 5-1411297-T-C is Benign according to our data. Variant chr5-1411297-T-C is described in ClinVar as Benign. ClinVar VariationId is 199052.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-6.82 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.498 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC6A3	NM_001044.5 link	c.1215A>G	p.Ser405Ser	synonymous_variant	Exon 9 of 15	ENST00000270349.12	NP_001035.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein
SLC6A3	ENST00000270349.12 link	c.1215A>G	p.Ser405Ser	synonymous_variant	Exon 9 of 15	1	NM_001044.5	ENSP00000270349.9
SLC6A3	ENST00000713696.1 link	c.1080A>G	p.Ser360Ser	synonymous_variant	Exon 8 of 15			ENSP00000519000.1
SLC6A3	ENST00000713697.1 link	n.*141-1448A>G		intron_variant	Intron 9 of 10			ENSP00000519001.1

Frequencies

GnomAD3 genomes

AF:

0.317

AC:

48154

AN:

151976

Hom.:

8740

Cov.:

show subpopulations

Gnomad AFR

AF:

0.504

Gnomad AMI

AF:

0.233

Gnomad AMR

AF:

0.202

Gnomad ASJ

AF:

0.213

Gnomad EAS

AF:

0.113

Gnomad SAS

AF:

0.172

Gnomad FIN

AF:

0.246

Gnomad MID

AF:

0.259

Gnomad NFE

AF:

0.273

Gnomad OTH

AF:

0.278

GnomAD2 exomes

AF:

0.231

AC:

37638

AN:

162704

AF XY:

0.228

show subpopulations

Gnomad AFR exome

AF:

0.505

Gnomad AMR exome

AF:

0.141

Gnomad ASJ exome

AF:

0.227

Gnomad EAS exome

AF:

0.111

Gnomad FIN exome

AF:

0.254

Gnomad NFE exome

AF:

0.267

Gnomad OTH exome

AF:

0.250

GnomAD4 exome

AF:

0.261

AC:

366187

AN:

1402772

Hom.:

50504

Cov.:

AF XY:

0.259

AC XY:

179099

AN XY:

692308

show subpopulations

African (AFR)

AF:

0.520

AC:

16533

AN:

31788

American (AMR)

AF:

0.149

AC:

5426

AN:

36452

Ashkenazi Jewish (ASJ)

AF:

0.229

AC:

5770

AN:

25206

East Asian (EAS)

AF:

0.0993

AC:

3597

AN:

36222

South Asian (SAS)

AF:

0.173

AC:

13723

AN:

79434

European-Finnish (FIN)

AF:

0.257

AC:

12536

AN:

48692

Middle Eastern (MID)

AF:

0.254

AC:

1447

AN:

5700

European-Non Finnish (NFE)

AF:

0.270

AC:

291871

AN:

1081132

Other (OTH)

AF:

0.263

AC:

15284

AN:

58146

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.491

Heterozygous variant carriers

15416

30833

46249

61666

77082

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

9826

19652

29478

39304

49130

<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:

0.317

AC:

48202

AN:

152094

Hom.:

8750

Cov.:

AF XY:

0.310

AC XY:

23069

AN XY:

74344

show subpopulations

African (AFR)

AF:

0.504

AC:

20912

AN:

41480

American (AMR)

AF:

0.202

AC:

3088

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.213

AC:

740

AN:

3468

East Asian (EAS)

AF:

0.113

AC:

584

AN:

5172

South Asian (SAS)

AF:

0.172

AC:

828

AN:

4826

European-Finnish (FIN)

AF:

0.246

AC:

2603

AN:

10586

Middle Eastern (MID)

AF:

0.262

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.273

AC:

18579

AN:

67952

Other (OTH)

AF:

0.274

AC:

579

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.527

Heterozygous variant carriers

1699

3398

5097

6796

8495

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

448

896

1344

1792

2240

<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:

0.283

Hom.:

15706

Bravo

AF:

0.321

Asia WGS

AF:

0.163

AC:

566

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:6

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 06, 2016

Genome Diagnostics Laboratory, Amsterdam University Medical Center

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

not provided

Benign:2

Aug 29, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is associated with the following publications: (PMID: 19183461, 28176268, 11704422, 15380858, 24211691, 10762168) -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

not specified

Benign:1

May 21, 2015

Eurofins Ntd Llc (ga)

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

-0.96

CADD

Benign

0.057

(source)

DANN

Benign

0.50

PhyloP100

-6.8

Mutation Taster

=99/1

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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