rs37020

Variant names:

• chr5-1418259-A-C
• rs37020
• NM_001044.5:c.928-2058T>G

Your query was ambiguous. Multiple possible variants found:

• chr5-1418259-A-C
• chr5-1418259-A-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001044.5(SLC6A3):​c.928-2058T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.531 in 152,000 control chromosomes in the GnomAD database, including 22,140 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.53 (22140 hom., cov: 33)
• Consequence: SLC6A3 NM_001044.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0840
• Publications: 19 publications found

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 Gene-Disease associations (from GenCC):

• classic dopamine transporter deficiency syndrome

  Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P
• SLC6A3-related dopamine transporter deficiency syndrome

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• parkinsonism-dystonia, infantile

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.02).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.651 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC6A3	NM_001044.5	c.928-2058T>G		intron_variant	Intron 6 of 14	ENST00000270349.12	NP_001035.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC6A3	ENST00000270349.12	c.928-2058T>G		intron_variant	Intron 6 of 14	1	NM_001044.5	ENSP00000270349.9
SLC6A3	ENST00000713696.1	c.793-2058T>G		intron_variant	Intron 5 of 14			ENSP00000519000.1
SLC6A3	ENST00000713697.1	n.928-2058T>G		intron_variant	Intron 6 of 10			ENSP00000519001.1

Frequencies

GnomAD3 genomes AF: 0.530 AC: 80551 AN: 151880 Hom.: 22103 Cov.: 33

Gnomad AFR AF: 0.641

Gnomad AMI AF: 0.410

Gnomad AMR AF: 0.546

Gnomad ASJ AF: 0.487

Gnomad EAS AF: 0.650

Gnomad SAS AF: 0.670

Gnomad FIN AF: 0.555

Gnomad MID AF: 0.500

Gnomad NFE AF: 0.441

Gnomad OTH AF: 0.498

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.531 AC: 80647 AN: 152000 Hom.: 22140 Cov.: 33 AF XY: 0.539 AC XY: 40068 AN XY: 74296

African (AFR) AF: 0.641 AC: 26577 AN: 41448

American (AMR) AF: 0.547 AC: 8357 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.487 AC: 1691 AN: 3472

East Asian (EAS) AF: 0.651 AC: 3361 AN: 5166

South Asian (SAS) AF: 0.670 AC: 3226 AN: 4816

European-Finnish (FIN) AF: 0.555 AC: 5874 AN: 10582

Middle Eastern (MID) AF: 0.493 AC: 145 AN: 294

European-Non Finnish (NFE) AF: 0.441 AC: 29983 AN: 67916

Other (OTH) AF: 0.503 AC: 1061 AN: 2110

Alfa AF: 0.502 Hom.: 2436

Bravo AF: 0.528

Asia WGS AF: 0.669 AC: 2324 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	4.9
DANN	Benign	0.55
PhyloP100		0.084
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs37020; hg19: chr5-1418374;