Variant chr5-1416027-C-A 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.1031+71G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.837 in 1,168,044 control chromosomes in the GnomAD database, including 411,503 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.81 ( 49818 hom., cov: 34)

Exomes 𝑓: 0.84 ( 361685 hom. )

Consequence

SLC6A3
NM_001044.5 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -3.14

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=-0.99).

BP6

Variant 5-1416027-C-A is Benign according to our data. Variant chr5-1416027-C-A is described in ClinVar as [Benign]. Clinvar id is 1185399.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.85 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.1031+71G>T		intron_variant		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.1031+71G>T		intron_variant		1	NM_001044.5	ENSP00000270349	P1
SLC6A3	ENST00000511750.1 linkuse as main transcript	n.481+71G>T		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes

AF:

0.806

AC:

122555

AN:

152074

Hom.:

49793

Cov.:

show subpopulations

Gnomad AFR

AF:

0.717

Gnomad AMI

AF:

0.843

Gnomad AMR

AF:

0.812

Gnomad ASJ

AF:

0.817

Gnomad EAS

AF:

0.631

Gnomad SAS

AF:

0.861

Gnomad FIN

AF:

0.882

Gnomad MID

AF:

0.763

Gnomad NFE

AF:

0.855

Gnomad OTH

AF:

0.801

GnomAD4 exome

AF:

0.842

AC:

855511

AN:

1015852

Hom.:

361685

AF XY:

0.845

AC XY:

442322

AN XY:

523706

show subpopulations

Gnomad4 AFR exome

AF:

0.711

Gnomad4 AMR exome

AF:

0.778

Gnomad4 ASJ exome

AF:

0.819

Gnomad4 EAS exome

AF:

0.634

Gnomad4 SAS exome

AF:

0.873

Gnomad4 FIN exome

AF:

0.894

Gnomad4 NFE exome

AF:

0.857

Gnomad4 OTH exome

AF:

0.829

GnomAD4 genome

AF:

0.806

AC:

122629

AN:

152192

Hom.:

49818

Cov.:

AF XY:

0.809

AC XY:

60209

AN XY:

74408

show subpopulations

Gnomad4 AFR

AF:

0.717

Gnomad4 AMR

AF:

0.813

Gnomad4 ASJ

AF:

0.817

Gnomad4 EAS

AF:

0.632

Gnomad4 SAS

AF:

0.859

Gnomad4 FIN

AF:

0.882

Gnomad4 NFE

AF:

0.855

Gnomad4 OTH

AF:

0.802

Alfa

AF:

0.835

Hom.:

14358

Bravo

AF:

0.790

Asia WGS

AF:

0.764

AC:

2660

AN:

3478

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	- -

Classic dopamine transporter deficiency syndrome

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 14, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.99

CADD

Benign

0.0080

DANN

Benign

0.48

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