rs6347

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001044.5(SLC6A3):c.1215A>G(p.Ser405=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.267 in 1,554,866 control chromosomes in the GnomAD database, including 59,254 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.32 ( 8750 hom., cov: 33)

Exomes 𝑓: 0.26 ( 50504 hom. )

Consequence

SLC6A3
NM_001044.5 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -6.82

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.96).

BP6

Variant 5-1411297-T-C is Benign according to our data. Variant chr5-1411297-T-C is described in ClinVar as [Benign]. Clinvar id is 199052.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-1411297-T-C is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-6.82 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.498 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC6A3	NM_001044.5 linkuse as main transcript	c.1215A>G	p.Ser405=	synonymous_variant	9/15	ENST00000270349.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC6A3	ENST00000270349.12 linkuse as main transcript	c.1215A>G	p.Ser405=	synonymous_variant	9/15	1	NM_001044.5	P1

Frequencies

GnomAD3 genomes

AF:

0.317

AC:

48154

AN:

151976

Hom.:

8740

Cov.:

show subpopulations

Gnomad AFR

AF:

0.504

Gnomad AMI

AF:

0.233

Gnomad AMR

AF:

0.202

Gnomad ASJ

AF:

0.213

Gnomad EAS

AF:

0.113

Gnomad SAS

AF:

0.172

Gnomad FIN

AF:

0.246

Gnomad MID

AF:

0.259

Gnomad NFE

AF:

0.273

Gnomad OTH

AF:

0.278

GnomAD3 exomes

AF:

0.231

AC:

37638

AN:

162704

Hom.:

5121

AF XY:

0.228

AC XY:

19568

AN XY:

86010

show subpopulations

Gnomad AFR exome

AF:

0.505

Gnomad AMR exome

AF:

0.141

Gnomad ASJ exome

AF:

0.227

Gnomad EAS exome

AF:

0.111

Gnomad SAS exome

AF:

0.170

Gnomad FIN exome

AF:

0.254

Gnomad NFE exome

AF:

0.267

Gnomad OTH exome

AF:

0.250

GnomAD4 exome

AF:

0.261

AC:

366187

AN:

1402772

Hom.:

50504

Cov.:

AF XY:

0.259

AC XY:

179099

AN XY:

692308

show subpopulations

Gnomad4 AFR exome

AF:

0.520

Gnomad4 AMR exome

AF:

0.149

Gnomad4 ASJ exome

AF:

0.229

Gnomad4 EAS exome

AF:

0.0993

Gnomad4 SAS exome

AF:

0.173

Gnomad4 FIN exome

AF:

0.257

Gnomad4 NFE exome

AF:

0.270

Gnomad4 OTH exome

AF:

0.263

GnomAD4 genome

AF:

0.317

AC:

48202

AN:

152094

Hom.:

8750

Cov.:

AF XY:

0.310

AC XY:

23069

AN XY:

74344

show subpopulations

Gnomad4 AFR

AF:

0.504

Gnomad4 AMR

AF:

0.202

Gnomad4 ASJ

AF:

0.213

Gnomad4 EAS

AF:

0.113

Gnomad4 SAS

AF:

0.172

Gnomad4 FIN

AF:

0.246

Gnomad4 NFE

AF:

0.273

Gnomad4 OTH

AF:

0.274

Alfa

AF:

0.272

Hom.:

5157

Bravo

AF:

0.321

Asia WGS

AF:

0.163

AC:

566

AN:

3478

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

Benign, no assertion criteria provided	clinical testing	Genome Diagnostics Laboratory, Amsterdam University Medical Center	Apr 06, 2016	- -
Benign, criteria provided, single submitter	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	Sep 21, 2015	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Eurofins Ntd Llc (ga)

May 21, 2015

- -

Parkinsonism-dystonia, infantile

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Feb 01, 2024

- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Aug 29, 2018

This variant is associated with the following publications: (PMID: 19183461, 28176268, 11704422, 15380858, 24211691, 10762168) -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.96

Cadd

Benign

0.057

Dann

Benign

0.50

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over