rs6350

chr5-1443084-G-Achr5-1443084-G-C

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -0.485

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 -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	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	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.: 33

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

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.: 34 AF XY: 0.0646 AC XY: 46946 AN XY: 727234

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.: 33 AF XY: 0.0602 AC XY: 4485 AN XY: 74456

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:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Classic dopamine transporter deficiency syndrome Benign:2

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

Parkinsonism-dystonia, infantile Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 31, 2024

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Aug 14, 2018

- -

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

Other links and lift over

dbSNP: rs6350; hg19: chr5-1443199;