rs6351

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_001044.5(SLC6A3):c.162C>T(p.Pro54Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0103 in 1,614,186 control chromosomes in the GnomAD database, including 111 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Synonymous variant affecting the same amino acid position (i.e. P54P) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.0064 ( 6 hom., cov: 33)

Exomes 𝑓: 0.011 ( 105 hom. )

Consequence

SLC6A3
NM_001044.5 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: -0.268

Publications

9 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=-0.81).

BP6

Variant 5-1443036-G-A is Benign according to our data. Variant chr5-1443036-G-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 470636.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.268 with no splicing effect.

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.00638 (971/152296) while in subpopulation NFE AF = 0.0109 (742/68012). AF 95% confidence interval is 0.0103. There are 6 homozygotes in GnomAd4. There are 455 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 6 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC6A3	NM_001044.5 link	c.162C>T	p.Pro54Pro	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.162C>T	p.Pro54Pro	synonymous_variant	Exon 2 of 15	1	NM_001044.5	ENSP00000270349.9	Q01959
SLC6A3	ENST00000713696.1 link	c.162C>T	p.Pro54Pro	synonymous_variant	Exon 2 of 15			ENSP00000519000.1
SLC6A3	ENST00000713698.1 link	c.162C>T	p.Pro54Pro	synonymous_variant	Exon 2 of 5			ENSP00000519002.1
SLC6A3	ENST00000713697.1 link	n.162C>T		non_coding_transcript_exon_variant	Exon 2 of 11			ENSP00000519001.1

Frequencies

GnomAD3 genomes

AF:

0.00639

AC:

972

AN:

152178

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00193

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00399

Gnomad ASJ

AF:

0.000865

Gnomad EAS

AF:

0.000579

Gnomad SAS

AF:

0.00786

Gnomad FIN

AF:

0.00301

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.0109

Gnomad OTH

AF:

0.00525

GnomAD2 exomes

AF:

0.00704

AC:

1769

AN:

251378

AF XY:

0.00761

show subpopulations

Gnomad AFR exome

AF:

0.00234

Gnomad AMR exome

AF:

0.00298

Gnomad ASJ exome

AF:

0.00169

Gnomad EAS exome

AF:

0.00103

Gnomad FIN exome

AF:

0.00333

Gnomad NFE exome

AF:

0.0107

Gnomad OTH exome

AF:

0.00587

GnomAD4 exome

AF:

0.0107

AC:

15663

AN:

1461890

Hom.:

105

Cov.:

AF XY:

0.0107

AC XY:

7772

AN XY:

727244

show subpopulations

African (AFR)

AF:

0.00122

AC:

AN:

33480

American (AMR)

AF:

0.00356

AC:

159

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00176

AC:

AN:

26136

East Asian (EAS)

AF:

0.00262

AC:

104

AN:

39700

South Asian (SAS)

AF:

0.00988

AC:

852

AN:

86258

European-Finnish (FIN)

AF:

0.00477

AC:

255

AN:

53418

Middle Eastern (MID)

AF:

0.00381

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.0122

AC:

13610

AN:

1112010

Other (OTH)

AF:

0.00950

AC:

574

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.485

Heterozygous variant carriers

974

1948

2921

3895

4869

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

526

1052

1578

2104

2630

<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:

0.00638

AC:

971

AN:

152296

Hom.:

Cov.:

AF XY:

0.00611

AC XY:

455

AN XY:

74478

show subpopulations

African (AFR)

AF:

0.00192

AC:

AN:

41562

American (AMR)

AF:

0.00399

AC:

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.000865

AC:

AN:

3470

East Asian (EAS)

AF:

0.000580

AC:

AN:

5170

South Asian (SAS)

AF:

0.00766

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00301

AC:

AN:

10624

Middle Eastern (MID)

AF:

0.00680

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0109

AC:

742

AN:

68012

Other (OTH)

AF:

0.00520

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

139

186

232

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<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:

0.00818

Hom.:

Bravo

AF:

0.00656

Asia WGS

AF:

0.00202

AC:

AN:

3478

EpiCase

AF:

0.0104

EpiControl

AF:

0.0102

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Mar 01, 2025

CeGaT Center for Human Genetics Tuebingen

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

SLC6A3: BP4, BP7, BS1, BS2 -

Oct 05, 2020

GeneDx

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Genome Diagnostics Laboratory, Amsterdam University Medical Center

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Classic dopamine transporter deficiency syndrome

Benign:2

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Jun 28, 2017

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

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Parkinsonism-dystonia, infantile

Benign:1

Feb 02, 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

-0.81

CADD

Benign

1.1

(source)

DANN

Benign

0.59

PhyloP100

-0.27

Mutation Taster

=100/0

polymorphism

(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