rs11564771

Variant names:

• chr5-1398682-G-A
• rs11564771
• NM_001044.5:c.1839+2233C>T

Your query was ambiguous. Multiple possible variants found:

• chr5-1398682-G-A
• chr5-1398682-G-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.1839+2233C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0933 in 152,154 control chromosomes in the GnomAD database, including 817 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 0.093 (817 hom., cov: 33)
• Consequence: SLC6A3 NM_001044.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.189
• Publications: 3 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=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.158 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC6A3	NM_001044.5	c.1839+2233C>T		intron_variant	Intron 14 of 14	ENST00000270349.12	NP_001035.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC6A3	ENST00000270349.12	c.1839+2233C>T		intron_variant	Intron 14 of 14	1	NM_001044.5	ENSP00000270349.9
SLC6A3	ENST00000512002.2	n.220+2233C>T		intron_variant	Intron 2 of 2	1
SLC6A3	ENST00000713696.1	c.*34+2233C>T		intron_variant	Intron 14 of 14			ENSP00000519000.1

Frequencies

GnomAD3 genomes AF: 0.0932 AC: 14174 AN: 152036 Hom.: 816 Cov.: 33

Gnomad AFR AF: 0.161

Gnomad AMI AF: 0.135

Gnomad AMR AF: 0.0457

Gnomad ASJ AF: 0.0524

Gnomad EAS AF: 0.00135

Gnomad SAS AF: 0.0274

Gnomad FIN AF: 0.0844

Gnomad MID AF: 0.0665

Gnomad NFE AF: 0.0778

Gnomad OTH AF: 0.0714

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

GnomAD4 genome AF: 0.0933 AC: 14195 AN: 152154 Hom.: 817 Cov.: 33 AF XY: 0.0901 AC XY: 6699 AN XY: 74386

African (AFR) AF: 0.162 AC: 6697 AN: 41464

American (AMR) AF: 0.0456 AC: 698 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.0524 AC: 182 AN: 3470

East Asian (EAS) AF: 0.00135 AC: 7 AN: 5188

South Asian (SAS) AF: 0.0278 AC: 134 AN: 4820

European-Finnish (FIN) AF: 0.0844 AC: 894 AN: 10598

Middle Eastern (MID) AF: 0.0646 AC: 19 AN: 294

European-Non Finnish (NFE) AF: 0.0778 AC: 5292 AN: 67998

Other (OTH) AF: 0.0706 AC: 149 AN: 2110

Alfa AF: 0.0797 Hom.: 450

Bravo AF: 0.0927

Asia WGS AF: 0.0260 AC: 90 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	1.4
DANN	Benign	0.45
PhyloP100		0.19
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: rs11564771; hg19: chr5-1398797;