Variant rs6349 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_ModerateBP6_Very_StrongBA1

The ENST00000270349.12(SLC6A3):c.1731C>T(p.Ala577=) 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
ENST00000270349.12 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: 3.04

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 -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 id is 287682.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-1402958-G-A is described in Lovd as [Benign].

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/exons	MANE	Protein	UniProt
SLC6A3	NM_001044.5 linkuse as main transcript	c.1731C>T	p.Ala577=	synonymous_variant	13/15	ENST00000270349.12	NP_001035.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC6A3	ENST00000270349.12 linkuse as main transcript	c.1731C>T	p.Ala577=	synonymous_variant	13/15	1	NM_001044.5	ENSP00000270349	P1

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

GnomAD3 exomes

AF:

0.0124

AC:

3116

AN:

250924

Hom.:

AF XY:

0.0110

AC XY:

1491

AN XY:

135792

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 SAS exome

AF:

0.0135

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

Gnomad4 AFR exome

AF:

0.0888

Gnomad4 AMR exome

AF:

0.0104

Gnomad4 ASJ exome

AF:

0.0456

Gnomad4 EAS exome

AF:

0.000252

Gnomad4 SAS exome

AF:

0.0130

Gnomad4 FIN exome

AF:

0.00114

Gnomad4 NFE exome

AF:

0.00259

Gnomad4 OTH exome

AF:

0.0123

GnomAD4 genome

AF:

0.0275

AC:

4189

AN:

152302

Hom.:

154

Cov.:

AF XY:

0.0264

AC XY:

1966

AN XY:

74486

show subpopulations

Gnomad4 AFR

AF:

0.0830

Gnomad4 AMR

AF:

0.0138

Gnomad4 ASJ

AF:

0.0484

Gnomad4 EAS

AF:

0.000578

Gnomad4 SAS

AF:

0.0153

Gnomad4 FIN

AF:

0.00113

Gnomad4 NFE

AF:

0.00329

Gnomad4 OTH

AF:

0.0208

Alfa

AF:

0.0170

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

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Aug 17, 2018	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Eurofins Ntd Llc (ga)

Apr 21, 2016

- -

Parkinsonism-dystonia, infantile

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 26, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.42

CADD

Benign

DANN

Benign

0.80

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

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