rs11564773

Variant names:

• chr5-1396698-T-C
• rs11564773
• NM_001044.5:c.1840-1940A>G

Variant summary

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

The NM_001044.5(SLC6A3):​c.1840-1940A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.107 in 152,100 control chromosomes in the GnomAD database, including 1,159 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 0.11 (1159 hom., cov: 32)
• Consequence: SLC6A3 NM_001044.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.74
• Publications: 5 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=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.194 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001044.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC6A3	NM_001044.5	MANE Select	c.1840-1940A>G		intron	N/A	NP_001035.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC6A3	ENST00000270349.12	TSL:1 MANE Select	c.1840-1940A>G		intron	N/A	ENSP00000270349.9
	SLC6A3	ENST00000512002.2	TSL:1	n.221-1940A>G		intron	N/A
	SLC6A3	ENST00000713696.1		c.*35-1940A>G		intron	N/A	ENSP00000519000.1

Frequencies

GnomAD3 genomes AF: 0.107 AC: 16235 AN: 151982 Hom.: 1156 Cov.: 32

Gnomad AFR AF: 0.197

Gnomad AMI AF: 0.137

Gnomad AMR AF: 0.0515

Gnomad ASJ AF: 0.0499

Gnomad EAS AF: 0.0224

Gnomad SAS AF: 0.0756

Gnomad FIN AF: 0.0849

Gnomad MID AF: 0.0696

Gnomad NFE AF: 0.0796

Gnomad OTH AF: 0.0813

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

GnomAD4 genome AF: 0.107 AC: 16268 AN: 152100 Hom.: 1159 Cov.: 32 AF XY: 0.104 AC XY: 7721 AN XY: 74340

African (AFR) AF: 0.198 AC: 8204 AN: 41502

American (AMR) AF: 0.0513 AC: 784 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.0499 AC: 173 AN: 3468

East Asian (EAS) AF: 0.0225 AC: 116 AN: 5162

South Asian (SAS) AF: 0.0765 AC: 368 AN: 4812

European-Finnish (FIN) AF: 0.0849 AC: 899 AN: 10584

Middle Eastern (MID) AF: 0.0680 AC: 20 AN: 294

European-Non Finnish (NFE) AF: 0.0796 AC: 5409 AN: 67978

Other (OTH) AF: 0.0805 AC: 170 AN: 2112

Alfa AF: 0.102 Hom.: 126

Bravo AF: 0.107

Asia WGS AF: 0.0580 AC: 200 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.23
DANN	Benign	0.18
PhyloP100		-1.7
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: rs11564773; hg19: chr5-1396813;