Variant 5-1443084-G-A details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_001044.5(SLC6A3):c.114C>T(p.Asn38=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0642 in 1,614,116 control chromosomes in the GnomAD database, including 3,584 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.059 ( 275 hom., cov: 33)

Exomes 𝑓: 0.065 ( 3309 hom. )

Consequence

SLC6A3
NM_001044.5 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.485

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=-0.74).

BP6

Variant 5-1443084-G-A is Benign according to our data. Variant chr5-1443084-G-A is described in ClinVar as [Benign]. Clinvar id is 522348.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-1443084-G-A is described in Lovd as [Likely_benign]. Variant chr5-1443084-G-A is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-0.485 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0623 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.114C>T	p.Asn38=	synonymous_variant	2/15	ENST00000270349.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC6A3	ENST00000270349.12 linkuse as main transcript	c.114C>T	p.Asn38=	synonymous_variant	2/15	1	NM_001044.5	P1

Frequencies

GnomAD3 genomes

AF:

0.0587

AC:

8935

AN:

152144

Hom.:

275

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0508

Gnomad AMI

AF:

0.0846

Gnomad AMR

AF:

0.0557

Gnomad ASJ

AF:

0.0438

Gnomad EAS

AF:

0.0160

Gnomad SAS

AF:

0.0561

Gnomad FIN

AF:

0.0840

Gnomad MID

AF:

0.0886

Gnomad NFE

AF:

0.0639

Gnomad OTH

AF:

0.0630

GnomAD3 exomes

AF:

0.0556

AC:

13978

AN:

251432

Hom.:

483

AF XY:

0.0574

AC XY:

7801

AN XY:

135908

show subpopulations

Gnomad AFR exome

AF:

0.0516

Gnomad AMR exome

AF:

0.0343

Gnomad ASJ exome

AF:

0.0416

Gnomad EAS exome

AF:

0.0184

Gnomad SAS exome

AF:

0.0596

Gnomad FIN exome

AF:

0.0805

Gnomad NFE exome

AF:

0.0639

Gnomad OTH exome

AF:

0.0588

GnomAD4 exome

AF:

0.0648

AC:

94667

AN:

1461854

Hom.:

3309

Cov.:

AF XY:

0.0646

AC XY:

46946

AN XY:

727234

show subpopulations

Gnomad4 AFR exome

AF:

0.0490

Gnomad4 AMR exome

AF:

0.0365

Gnomad4 ASJ exome

AF:

0.0417

Gnomad4 EAS exome

AF:

0.0128

Gnomad4 SAS exome

AF:

0.0608

Gnomad4 FIN exome

AF:

0.0779

Gnomad4 NFE exome

AF:

0.0684

Gnomad4 OTH exome

AF:

0.0646

GnomAD4 genome

AF:

0.0588

AC:

8950

AN:

152262

Hom.:

275

Cov.:

AF XY:

0.0602

AC XY:

4485

AN XY:

74456

show subpopulations

Gnomad4 AFR

AF:

0.0510

Gnomad4 AMR

AF:

0.0556

Gnomad4 ASJ

AF:

0.0438

Gnomad4 EAS

AF:

0.0160

Gnomad4 SAS

AF:

0.0570

Gnomad4 FIN

AF:

0.0840

Gnomad4 NFE

AF:

0.0638

Gnomad4 OTH

AF:

0.0629

Alfa

AF:

0.0595

Hom.:

533

Bravo

AF:

0.0559

EpiCase

AF:

0.0692

EpiControl

AF:

0.0651

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

Likely benign, no assertion criteria provided	clinical testing	Genome Diagnostics Laboratory, Amsterdam University Medical Center	Apr 07, 2016	- -
Benign, criteria provided, single submitter	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	Sep 21, 2015	- -

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Aug 14, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Parkinsonism-dystonia, infantile

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 31, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.74

CADD

Benign

0.28

DANN

Benign

0.55

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