rs10052016

chr5-1427996-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001044.5(SLC6A3):c.653+4468T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.219 in 152,106 control chromosomes in the GnomAD database, including 3,768 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 0.22 (3768 hom., cov: 32)
• Consequence: SLC6A3 NM_001044.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.442

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.247 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC6A3	NM_001044.5	c.653+4468T>C		intron_variant		ENST00000270349.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC6A3	ENST00000270349.12	c.653+4468T>C		intron_variant		1	NM_001044.5	P1

Frequencies

GnomAD3 genomes AF: 0.219 AC: 33270 AN: 151988 Hom.: 3760 Cov.: 32

Gnomad AFR AF: 0.161

Gnomad AMI AF: 0.223

Gnomad AMR AF: 0.212

Gnomad ASJ AF: 0.225

Gnomad EAS AF: 0.133

Gnomad SAS AF: 0.243

Gnomad FIN AF: 0.287

Gnomad MID AF: 0.215

Gnomad NFE AF: 0.250

Gnomad OTH AF: 0.216

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

GnomAD4 genome AF: 0.219 AC: 33308 AN: 152106 Hom.: 3768 Cov.: 32 AF XY: 0.221 AC XY: 16410 AN XY: 74354

Gnomad4 AFR AF: 0.161

Gnomad4 AMR AF: 0.212

Gnomad4 ASJ AF: 0.225

Gnomad4 EAS AF: 0.133

Gnomad4 SAS AF: 0.244

Gnomad4 FIN AF: 0.287

Gnomad4 NFE AF: 0.250

Gnomad4 OTH AF: 0.220

Alfa AF: 0.234 Hom.: 702

Bravo AF: 0.208

Asia WGS AF: 0.219 AC: 763 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
Cadd	Benign	3.8
Dann	Benign	0.40

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

Publications

LitVar

Other links and lift over

dbSNP: rs10052016; hg19: chr5-1428111;