rs40358

chr5-1416027-C-Achr5-1416027-C-Gchr5-1416027-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -3.14

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]

ACMG classification

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	UniProt
SLC6A3	NM_001044.5	c.1031+71G>T		intron_variant		ENST00000270349.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC6A3	ENST00000270349.12	c.1031+71G>T		intron_variant		1	NM_001044.5	P1
SLC6A3	ENST00000511750.1	n.481+71G>T		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.806 AC: 122555 AN: 152074 Hom.: 49793 Cov.: 34

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

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.: 34 AF XY: 0.809 AC XY: 60209 AN XY: 74408

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:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Classic dopamine transporter deficiency syndrome Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 14, 2021

- -

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	-0.99
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

Other links and lift over

dbSNP: rs40358; hg19: chr5-1416142; COSMIC: COSV54365179;