chr5-1392596-G-A

Variant names:

• chr5-1392596-G-A
• rs3863145
• NM_001044.5:c.*2139C>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.*2139C>T variant causes a downstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.207 in 151,614 control chromosomes in the GnomAD database, including 3,580 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 0.21 (3580 hom., cov: 31)
• Consequence: SLC6A3 NM_001044.5 downstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.56
• Publications: 10 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 (NFE) allele frequency at 95% confidence interval = 0.256 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC6A3	NM_001044.5	c.*2139C>T		downstream_gene_variant		ENST00000270349.12	NP_001035.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC6A3	ENST00000270349.12	c.*2139C>T		downstream_gene_variant		1	NM_001044.5	ENSP00000270349.9

Frequencies

GnomAD3 genomes AF: 0.207 AC: 31422 AN: 151498 Hom.: 3581 Cov.: 31

Gnomad AFR AF: 0.130

Gnomad AMI AF: 0.213

Gnomad AMR AF: 0.205

Gnomad ASJ AF: 0.399

Gnomad EAS AF: 0.0671

Gnomad SAS AF: 0.166

Gnomad FIN AF: 0.186

Gnomad MID AF: 0.383

Gnomad NFE AF: 0.260

Gnomad OTH AF: 0.249

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

GnomAD4 genome AF: 0.207 AC: 31420 AN: 151614 Hom.: 3580 Cov.: 31 AF XY: 0.204 AC XY: 15079 AN XY: 74074

African (AFR) AF: 0.130 AC: 5398 AN: 41406

American (AMR) AF: 0.205 AC: 3118 AN: 15244

Ashkenazi Jewish (ASJ) AF: 0.399 AC: 1387 AN: 3472

East Asian (EAS) AF: 0.0667 AC: 340 AN: 5098

South Asian (SAS) AF: 0.165 AC: 788 AN: 4774

European-Finnish (FIN) AF: 0.186 AC: 1956 AN: 10502

Middle Eastern (MID) AF: 0.395 AC: 116 AN: 294

European-Non Finnish (NFE) AF: 0.260 AC: 17608 AN: 67814

Other (OTH) AF: 0.245 AC: 516 AN: 2102

Alfa AF: 0.219 Hom.: 2376

Bravo AF: 0.208

Asia WGS AF: 0.110 AC: 382 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	0.27
DANN	Benign	0.56
PhyloP100		-3.6

Splicing

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

Other links and lift over

dbSNP: rs3863145; hg19: chr5-1392711;