Variant rs6348 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_001044.5(SLC6A3):c.810C>T(p.Ala270=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.014 in 1,613,388 control chromosomes in the GnomAD database, including 2,576 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.073 ( 1319 hom., cov: 33)

Exomes 𝑓: 0.0079 ( 1257 hom. )

Consequence

SLC6A3
NM_001044.5 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: 2.44

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 -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.4).

BP6

Variant 5-1420686-G-A is Benign according to our data. Variant chr5-1420686-G-A is described in ClinVar as [Benign]. Clinvar id is 470642.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-1420686-G-A is described in Lovd as [Likely_benign].

BP7

Synonymous conserved (PhyloP=2.43 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.247 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.810C>T	p.Ala270=	synonymous_variant	6/15	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.810C>T	p.Ala270=	synonymous_variant	6/15	1	NM_001044.5	ENSP00000270349	P1

Frequencies

GnomAD3 genomes

AF:

0.0725

AC:

11038

AN:

152180

Hom.:

1321

Cov.:

show subpopulations

Gnomad AFR

AF:

0.252

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0265

Gnomad ASJ

AF:

0.000576

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00518

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0348

Gnomad NFE

AF:

0.000999

Gnomad OTH

AF:

0.0463

GnomAD3 exomes

AF:

0.0199

AC:

4979

AN:

250576

Hom.:

568

AF XY:

0.0146

AC XY:

1986

AN XY:

135618

show subpopulations

Gnomad AFR exome

AF:

0.259

Gnomad AMR exome

AF:

0.0130

Gnomad ASJ exome

AF:

0.00110

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00549

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000814

Gnomad OTH exome

AF:

0.00948

GnomAD4 exome

AF:

0.00791

AC:

11560

AN:

1461090

Hom.:

1257

Cov.:

AF XY:

0.00697

AC XY:

5066

AN XY:

726794

show subpopulations

Gnomad4 AFR exome

AF:

0.261

Gnomad4 AMR exome

AF:

0.0146

Gnomad4 ASJ exome

AF:

0.000459

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00544

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000536

Gnomad4 OTH exome

AF:

0.0169

GnomAD4 genome

AF:

0.0725

AC:

11049

AN:

152298

Hom.:

1319

Cov.:

AF XY:

0.0698

AC XY:

5200

AN XY:

74480

show subpopulations

Gnomad4 AFR

AF:

0.251

Gnomad4 AMR

AF:

0.0265

Gnomad4 ASJ

AF:

0.000576

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00518

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00100

Gnomad4 OTH

AF:

0.0458

Alfa

AF:

0.0224

Hom.:

490

Bravo

AF:

0.0830

Asia WGS

AF:

0.0120

AC:

AN:

3478

EpiCase

AF:

0.00120

EpiControl

AF:

0.00113

ClinVar

Significance: Benign

Submissions summary: Benign:3

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	Jul 05, 2018	- -

Parkinsonism-dystonia, infantile

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 30, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.40

CADD

Benign

DANN

Benign

0.75

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