rs8179029

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001044.5(SLC6A3):c.1270-21G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.18 in 1,612,242 control chromosomes in the GnomAD database, including 27,806 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). There are indicators that this mutation may affect the branch point..

Frequency

Genomes: 𝑓 0.15 ( 1920 hom., cov: 33)

Exomes 𝑓: 0.18 ( 25886 hom. )

Consequence

SLC6A3
NM_001044.5 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -3.05

Publications

15 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), G2P, PanelApp Australia, Ambry Genetics
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 -20 ACMG points.

BP4

This position, referring to a specific DNA site, is a probable branch point but is likely benign (scored 1 / 10, using the threshold of <=3). The score ranges from 0 to 10, with values ≤3 considered benign and >5 classified as pathogenic. Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BP6

Variant 5-1409870-C-T is Benign according to our data. Variant chr5-1409870-C-T is described in ClinVar as Benign. ClinVar VariationId is 1180099.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.199 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001044.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC6A3	NM_001044.5	MANE Select	c.1270-21G>A		intron	N/A	NP_001035.1	Q01959

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
SLC6A3	ENST00000270349.12	TSL:1 MANE Select	c.1270-21G>A	intron	N/A	ENSP00000270349.9	Q01959
SLC6A3	ENST00000941790.1		c.1135-21G>A	intron	N/A	ENSP00000611849.1
SLC6A3	ENST00000713696.1		c.1135-21G>A	intron	N/A	ENSP00000519000.1	A0AAQ5BGN6

Frequencies

GnomAD3 genomes

AF:

0.148

AC:

22541

AN:

152120

Hom.:

1922

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0719

Gnomad AMI

AF:

0.197

Gnomad AMR

AF:

0.131

Gnomad ASJ

AF:

0.167

Gnomad EAS

AF:

0.0782

Gnomad SAS

AF:

0.127

Gnomad FIN

AF:

0.156

Gnomad MID

AF:

0.197

Gnomad NFE

AF:

0.202

Gnomad OTH

AF:

0.169

GnomAD2 exomes

AF:

0.155

AC:

38581

AN:

249542

AF XY:

0.158

show subpopulations

Gnomad AFR exome

AF:

0.0695

Gnomad AMR exome

AF:

0.0991

Gnomad ASJ exome

AF:

0.177

Gnomad EAS exome

AF:

0.0713

Gnomad FIN exome

AF:

0.159

Gnomad NFE exome

AF:

0.202

Gnomad OTH exome

AF:

0.187

GnomAD4 exome

AF:

0.183

AC:

267607

AN:

1460004

Hom.:

25886

Cov.:

AF XY:

0.183

AC XY:

132685

AN XY:

726278

show subpopulations

African (AFR)

AF:

0.0701

AC:

2345

AN:

33472

American (AMR)

AF:

0.102

AC:

4572

AN:

44720

Ashkenazi Jewish (ASJ)

AF:

0.178

AC:

4649

AN:

26128

East Asian (EAS)

AF:

0.0560

AC:

2224

AN:

39698

South Asian (SAS)

AF:

0.125

AC:

10779

AN:

86244

European-Finnish (FIN)

AF:

0.164

AC:

8537

AN:

52002

Middle Eastern (MID)

AF:

0.209

AC:

1199

AN:

5740

European-Non Finnish (NFE)

AF:

0.200

AC:

222476

AN:

1111640

Other (OTH)

AF:

0.179

AC:

10826

AN:

60360

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.467

Heterozygous variant carriers

11247

22494

33741

44988

56235

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

7548

15096

22644

30192

37740

<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:

0.148

AC:

22542

AN:

152238

Hom.:

1920

Cov.:

AF XY:

0.145

AC XY:

10819

AN XY:

74450

show subpopulations

African (AFR)

AF:

0.0720

AC:

2993

AN:

41548

American (AMR)

AF:

0.131

AC:

2006

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.167

AC:

578

AN:

3468

East Asian (EAS)

AF:

0.0776

AC:

402

AN:

5180

South Asian (SAS)

AF:

0.128

AC:

615

AN:

4820

European-Finnish (FIN)

AF:

0.156

AC:

1656

AN:

10612

Middle Eastern (MID)

AF:

0.192

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.202

AC:

13706

AN:

68002

Other (OTH)

AF:

0.166

AC:

351

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

995

1991

2986

3982

4977

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

246

492

738

984

1230

<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:

0.169

Hom.:

1178

Bravo

AF:

0.143

Asia WGS

AF:

0.0910

AC:

318

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

6.8

(source)

DANN

Benign

0.41

PhyloP100

-3.1

BranchPoint Hunter

1.0

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

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

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over