Variant 5-1432710-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001044.5(SLC6A3):c.419-12C>A variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.251 in 1,605,626 control chromosomes in the GnomAD database, including 57,552 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.31 ( 8283 hom., cov: 32)

Exomes 𝑓: 0.25 ( 49269 hom. )

Consequence

SLC6A3
NM_001044.5 splice_polypyrimidine_tract, intron

Scores

Splicing: ADA: 0.00003653

Clinical Significance

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

Conservation

PhyloP100: 0.662

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BP6

Variant 5-1432710-G-T is Benign according to our data. Variant chr5-1432710-G-T is described in ClinVar as [Benign]. Clinvar id is 522347.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-1432710-G-T is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.508 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.419-12C>A		splice_polypyrimidine_tract_variant, intron_variant		ENST00000270349.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC6A3	ENST00000270349.12 linkuse as main transcript	c.419-12C>A		splice_polypyrimidine_tract_variant, intron_variant		1	NM_001044.5	P1

Frequencies

GnomAD3 genomes

AF:

0.311

AC:

47180

AN:

151876

Hom.:

8274

Cov.:

show subpopulations

Gnomad AFR

AF:

0.440

Gnomad AMI

AF:

0.204

Gnomad AMR

AF:

0.334

Gnomad ASJ

AF:

0.281

Gnomad EAS

AF:

0.525

Gnomad SAS

AF:

0.416

Gnomad FIN

AF:

0.294

Gnomad MID

AF:

0.282

Gnomad NFE

AF:

0.210

Gnomad OTH

AF:

0.282

GnomAD3 exomes

AF:

0.305

AC:

75405

AN:

246960

Hom.:

12962

AF XY:

0.304

AC XY:

40615

AN XY:

133678

show subpopulations

Gnomad AFR exome

AF:

0.449

Gnomad AMR exome

AF:

0.359

Gnomad ASJ exome

AF:

0.277

Gnomad EAS exome

AF:

0.516

Gnomad SAS exome

AF:

0.422

Gnomad FIN exome

AF:

0.291

Gnomad NFE exome

AF:

0.210

Gnomad OTH exome

AF:

0.255

GnomAD4 exome

AF:

0.245

AC:

356468

AN:

1453632

Hom.:

49269

Cov.:

AF XY:

0.250

AC XY:

180725

AN XY:

723554

show subpopulations

Gnomad4 AFR exome

AF:

0.449

Gnomad4 AMR exome

AF:

0.352

Gnomad4 ASJ exome

AF:

0.277

Gnomad4 EAS exome

AF:

0.529

Gnomad4 SAS exome

AF:

0.420

Gnomad4 FIN exome

AF:

0.285

Gnomad4 NFE exome

AF:

0.207

Gnomad4 OTH exome

AF:

0.268

GnomAD4 genome

AF:

0.311

AC:

47229

AN:

151994

Hom.:

8283

Cov.:

AF XY:

0.318

AC XY:

23605

AN XY:

74266

show subpopulations

Gnomad4 AFR

AF:

0.440

Gnomad4 AMR

AF:

0.334

Gnomad4 ASJ

AF:

0.281

Gnomad4 EAS

AF:

0.525

Gnomad4 SAS

AF:

0.415

Gnomad4 FIN

AF:

0.294

Gnomad4 NFE

AF:

0.210

Gnomad4 OTH

AF:

0.283

Alfa

AF:

0.227

Hom.:

8935

Bravo

AF:

0.317

Asia WGS

AF:

0.445

AC:

1546

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

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 19, 2015	- -
Benign, criteria provided, single submitter	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	Sep 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

Jul 05, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

Cadd

Benign

7.1

Dann

Benign

0.36

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000037

dbscSNV1_RF

Benign

0.012

SpliceAI score (max)

0.040

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