5-1443084-G-A

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.114C>T(p.Asn38Asn) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0642 in 1,614,116 control chromosomes in the GnomAD database, including 3,584 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.059 ( 275 hom., cov: 33)

Exomes 𝑓: 0.065 ( 3309 hom. )

Consequence

SLC6A3
NM_001044.5 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.485

Publications

49 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=-0.74).

BP6

Variant 5-1443084-G-A is Benign according to our data. Variant chr5-1443084-G-A is described in ClinVar as Benign. ClinVar VariationId is 522348.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.485 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0623 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC6A3	NM_001044.5 link	c.114C>T	p.Asn38Asn	synonymous_variant	Exon 2 of 15	ENST00000270349.12	NP_001035.1	Q01959

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
SLC6A3	ENST00000270349.12 link	c.114C>T	p.Asn38Asn	synonymous_variant	Exon 2 of 15	1	NM_001044.5	ENSP00000270349.9	Q01959
SLC6A3	ENST00000713696.1 link	c.114C>T	p.Asn38Asn	synonymous_variant	Exon 2 of 15			ENSP00000519000.1
SLC6A3	ENST00000713698.1 link	c.114C>T	p.Asn38Asn	synonymous_variant	Exon 2 of 5			ENSP00000519002.1
SLC6A3	ENST00000713697.1 link	n.114C>T		non_coding_transcript_exon_variant	Exon 2 of 11			ENSP00000519001.1

Frequencies

GnomAD3 genomes

AF:

0.0587

AC:

8935

AN:

152144

Hom.:

275

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0508

Gnomad AMI

AF:

0.0846

Gnomad AMR

AF:

0.0557

Gnomad ASJ

AF:

0.0438

Gnomad EAS

AF:

0.0160

Gnomad SAS

AF:

0.0561

Gnomad FIN

AF:

0.0840

Gnomad MID

AF:

0.0886

Gnomad NFE

AF:

0.0639

Gnomad OTH

AF:

0.0630

GnomAD2 exomes

AF:

0.0556

AC:

13978

AN:

251432

AF XY:

0.0574

show subpopulations

Gnomad AFR exome

AF:

0.0516

Gnomad AMR exome

AF:

0.0343

Gnomad ASJ exome

AF:

0.0416

Gnomad EAS exome

AF:

0.0184

Gnomad FIN exome

AF:

0.0805

Gnomad NFE exome

AF:

0.0639

Gnomad OTH exome

AF:

0.0588

GnomAD4 exome

AF:

0.0648

AC:

94667

AN:

1461854

Hom.:

3309

Cov.:

AF XY:

0.0646

AC XY:

46946

AN XY:

727234

show subpopulations

African (AFR)

AF:

0.0490

AC:

1640

AN:

33480

American (AMR)

AF:

0.0365

AC:

1631

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.0417

AC:

1090

AN:

26136

East Asian (EAS)

AF:

0.0128

AC:

507

AN:

39700

South Asian (SAS)

AF:

0.0608

AC:

5241

AN:

86258

European-Finnish (FIN)

AF:

0.0779

AC:

4160

AN:

53420

Middle Eastern (MID)

AF:

0.0824

AC:

475

AN:

5768

European-Non Finnish (NFE)

AF:

0.0684

AC:

76019

AN:

1111972

Other (OTH)

AF:

0.0646

AC:

3904

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.472

Heterozygous variant carriers

5431

10861

16292

21722

27153

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2828

5656

8484

11312

14140

<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:

0.0588

AC:

8950

AN:

152262

Hom.:

275

Cov.:

AF XY:

0.0602

AC XY:

4485

AN XY:

74456

show subpopulations

African (AFR)

AF:

0.0510

AC:

2118

AN:

41544

American (AMR)

AF:

0.0556

AC:

851

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.0438

AC:

152

AN:

3472

East Asian (EAS)

AF:

0.0160

AC:

AN:

5186

South Asian (SAS)

AF:

0.0570

AC:

275

AN:

4824

European-Finnish (FIN)

AF:

0.0840

AC:

891

AN:

10612

Middle Eastern (MID)

AF:

0.0952

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0638

AC:

4342

AN:

68008

Other (OTH)

AF:

0.0629

AC:

133

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

429

859

1288

1718

2147

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

102

204

306

408

510

<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:

0.0593

Hom.:

705

Bravo

AF:

0.0559

EpiCase

AF:

0.0692

EpiControl

AF:

0.0651

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

Apr 07, 2016

Genome Diagnostics Laboratory, Amsterdam University Medical Center

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

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

- -

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Aug 14, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Parkinsonism-dystonia, infantile

Benign:1

Feb 03, 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

-0.74

CADD

Benign

0.28

(source)

DANN

Benign

0.55

PhyloP100

-0.48

Mutation Taster

=100/0

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