rs9312866

Positions:

• chr5-1435987-G-A

Variant summary

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

The NM_001044.5(SLC6A3):​c.419-3289C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. 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 0.16 (2655 hom., cov: 19)
• Consequence: SLC6A3 NM_001044.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0560

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=-0.84).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.199 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC6A3	NM_001044.5	c.419-3289C>T		intron_variant		ENST00000270349.12	NP_001035.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC6A3	ENST00000270349.12	c.419-3289C>T		intron_variant		1	NM_001044.5	ENSP00000270349	P1

Frequencies

GnomAD3 genomes AF: 0.163 AC: 21386 AN: 131198 Hom.: 2649 Cov.: 19

Gnomad AFR AF: 0.0877

Gnomad AMI AF: 0.175

Gnomad AMR AF: 0.166

Gnomad ASJ AF: 0.178

Gnomad EAS AF: 0.0804

Gnomad SAS AF: 0.175

Gnomad FIN AF: 0.220

Gnomad MID AF: 0.181

Gnomad NFE AF: 0.202

Gnomad OTH AF: 0.167

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

GnomAD4 genome AF: 0.163 AC: 21413 AN: 131298 Hom.: 2655 Cov.: 19 AF XY: 0.163 AC XY: 10389 AN XY: 63580

Gnomad4 AFR AF: 0.0876

Gnomad4 AMR AF: 0.166

Gnomad4 ASJ AF: 0.178

Gnomad4 EAS AF: 0.0804

Gnomad4 SAS AF: 0.178

Gnomad4 FIN AF: 0.220

Gnomad4 NFE AF: 0.202

Gnomad4 OTH AF: 0.171

Alfa AF: 0.194 Hom.: 248

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	5.9
DANN	Benign	0.33

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: rs9312866; hg19: chr5-1436102;