chr5-1402958-G-A

Variant names:

Variant summary

Our verdict is Benign. The variant received -18 ACMG points: 0P and 18B. BP4_ModerateBP6_Very_StrongBA1

The NM_001044.5(SLC6A3):c.1731C>T(p.Ala577Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0085 in 1,614,000 control chromosomes in the GnomAD database, including 354 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.028 ( 154 hom., cov: 32)

Exomes 𝑓: 0.0065 ( 200 hom. )

Consequence

SLC6A3
NM_001044.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 3.04

Publications

5 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 -18 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.42).

BP6

Variant 5-1402958-G-A is Benign according to our data. Variant chr5-1402958-G-A is described in ClinVar as Benign. ClinVar VariationId is 287682.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0807 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC6A3	NM_001044.5 link	c.1731C>T	p.Ala577Ala	synonymous_variant	Exon 13 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.1731C>T	p.Ala577Ala	synonymous_variant	Exon 13 of 15	1	NM_001044.5	ENSP00000270349.9		Q01959
SLC6A3	ENST00000713696.1 link	c.1645C>T	p.Leu549Leu	synonymous_variant	Exon 13 of 15			ENSP00000519000.1

Frequencies

GnomAD3 genomes

AF:

0.0275

AC:

4182

AN:

152184

Hom.:

155

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0831

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0138

Gnomad ASJ

AF:

0.0484

Gnomad EAS

AF:

0.000577

Gnomad SAS

AF:

0.0151

Gnomad FIN

AF:

0.00113

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.00329

Gnomad OTH

AF:

0.0210

GnomAD2 exomes

AF:

0.0124

AC:

3116

AN:

250924

AF XY:

0.0110

show subpopulations

Gnomad AFR exome

AF:

0.0883

Gnomad AMR exome

AF:

0.00981

Gnomad ASJ exome

AF:

0.0458

Gnomad EAS exome

AF:

0.000381

Gnomad FIN exome

AF:

0.000833

Gnomad NFE exome

AF:

0.00322

Gnomad OTH exome

AF:

0.0134

GnomAD4 exome

AF:

0.00652

AC:

9532

AN:

1461698

Hom.:

200

Cov.:

AF XY:

0.00658

AC XY:

4781

AN XY:

727140

show subpopulations

African (AFR)

AF:

0.0888

AC:

2972

AN:

33480

American (AMR)

AF:

0.0104

AC:

465

AN:

44720

Ashkenazi Jewish (ASJ)

AF:

0.0456

AC:

1192

AN:

26136

East Asian (EAS)

AF:

0.000252

AC:

AN:

39700

South Asian (SAS)

AF:

0.0130

AC:

1122

AN:

86252

European-Finnish (FIN)

AF:

0.00114

AC:

AN:

53346

Middle Eastern (MID)

AF:

0.0145

AC:

AN:

5674

European-Non Finnish (NFE)

AF:

0.00259

AC:

2883

AN:

1112008

Other (OTH)

AF:

0.0123

AC:

745

AN:

60382

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.468

Heterozygous variant carriers

587

1174

1760

2347

2934

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

182

364

546

728

910

<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:

0.0275

AC:

4189

AN:

152302

Hom.:

154

Cov.:

AF XY:

0.0264

AC XY:

1966

AN XY:

74486

show subpopulations

African (AFR)

AF:

0.0830

AC:

3450

AN:

41548

American (AMR)

AF:

0.0138

AC:

211

AN:

15306

Ashkenazi Jewish (ASJ)

AF:

0.0484

AC:

168

AN:

3472

East Asian (EAS)

AF:

0.000578

AC:

AN:

5186

South Asian (SAS)

AF:

0.0153

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00113

AC:

AN:

10620

Middle Eastern (MID)

AF:

0.0102

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00329

AC:

224

AN:

68020

Other (OTH)

AF:

0.0208

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

200

400

599

799

999

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

138

184

230

<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:

0.0149

Hom.:

Bravo

AF:

0.0311

Asia WGS

AF:

0.0190

AC:

AN:

3478

EpiCase

AF:

0.00436

EpiControl

AF:

0.00439

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Aug 17, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

not specified

Benign:1

Apr 21, 2016

Eurofins Ntd Llc (ga)

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

-0.42

CADD

Benign

(source)

DANN

Benign

0.80

PhyloP100

3.0

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

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over