rs6346

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1

The NM_001044.5(SLC6A3):c.150G>T(p.Pro50Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00779 in 1,614,162 control chromosomes in the GnomAD database, including 842 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. P50P) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.040 ( 455 hom., cov: 33)

Exomes 𝑓: 0.0044 ( 387 hom. )

Consequence

SLC6A3
NM_001044.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -2.98

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 -16 ACMG points.

BP6

Variant 5-1443048-C-A is Benign according to our data. Variant chr5-1443048-C-A is described in ClinVar as [Benign]. Clinvar id is 470634.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.138 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC6A3	NM_001044.5 link	c.150G>T	p.Pro50Pro	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.150G>T	p.Pro50Pro	synonymous_variant	Exon 2 of 15	1	NM_001044.5	ENSP00000270349.9	Q01959
SLC6A3	ENST00000713696.1 link	c.150G>T	p.Pro50Pro	synonymous_variant	Exon 2 of 15			ENSP00000519000.1
SLC6A3	ENST00000713698.1 link	c.150G>T	p.Pro50Pro	synonymous_variant	Exon 2 of 5			ENSP00000519002.1
SLC6A3	ENST00000713697.1 link	n.150G>T		non_coding_transcript_exon_variant	Exon 2 of 11			ENSP00000519001.1

Frequencies

GnomAD3 genomes

AF:

0.0403

AC:

6138

AN:

152158

Hom.:

452

Cov.:

show subpopulations

Gnomad AFR

AF:

0.140

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0156

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000827

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000397

Gnomad OTH

AF:

0.0239

GnomAD2 exomes

AF:

0.0110

AC:

2773

AN:

251404

AF XY:

0.00816

show subpopulations

Gnomad AFR exome

AF:

0.147

Gnomad AMR exome

AF:

0.00836

Gnomad ASJ exome

AF:

0.000397

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000308

Gnomad OTH exome

AF:

0.00619

GnomAD4 exome

AF:

0.00438

AC:

6406

AN:

1461886

Hom.:

387

Cov.:

AF XY:

0.00380

AC XY:

2764

AN XY:

727242

show subpopulations

African (AFR)

AF:

0.153

AC:

5117

AN:

33480

American (AMR)

AF:

0.00888

AC:

397

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.000191

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.000429

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53416

Middle Eastern (MID)

AF:

0.00728

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.000221

AC:

246

AN:

1112008

Other (OTH)

AF:

0.00931

AC:

562

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.476

Heterozygous variant carriers

395

790

1184

1579

1974

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0405

AC:

6164

AN:

152276

Hom.:

455

Cov.:

AF XY:

0.0391

AC XY:

2915

AN XY:

74458

show subpopulations

African (AFR)

AF:

0.141

AC:

5842

AN:

41526

American (AMR)

AF:

0.0156

AC:

239

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.000288

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5178

South Asian (SAS)

AF:

0.000828

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10622

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000397

AC:

AN:

68030

Other (OTH)

AF:

0.0237

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

Heterozygous variant carriers

257

514

772

1029

1286

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0106

Hom.:

Bravo

AF:

0.0469

Asia WGS

AF:

0.00693

AC:

AN:

3478

EpiCase

AF:

0.000436

EpiControl

AF:

0.000415

ClinVar

Significance: Benign

Submissions summary: Benign:3

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

- -

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

-0.69

CADD

Benign

3.3

(source)

DANN

Benign

0.51

PhyloP100

-3.0

Mutation Taster

=99/1

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.25

Details are displayed if max score is > 0.2

DS_AG_spliceai

0.25

Position offset: -7

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

rs6346

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