5-1415514-A-T

Position:

• chr5-1415514-A-T

Variant summary

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

The NM_001044.5(SLC6A3):​c.1031+584T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.272 in 152,102 control chromosomes in the GnomAD database, including 6,568 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 0.27 (6568 hom., cov: 33)
• Consequence: SLC6A3 NM_001044.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.77

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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.469 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC6A3	NM_001044.5	c.1031+584T>A		intron_variant		ENST00000270349.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC6A3	ENST00000270349.12	c.1031+584T>A		intron_variant		1	NM_001044.5	P1
SLC6A3	ENST00000511750.1	n.481+584T>A		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.271 AC: 41256 AN: 151984 Hom.: 6552 Cov.: 33

Gnomad AFR AF: 0.412

Gnomad AMI AF: 0.107

Gnomad AMR AF: 0.287

Gnomad ASJ AF: 0.224

Gnomad EAS AF: 0.485

Gnomad SAS AF: 0.290

Gnomad FIN AF: 0.243

Gnomad MID AF: 0.237

Gnomad NFE AF: 0.175

Gnomad OTH AF: 0.235

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

GnomAD4 genome AF: 0.272 AC: 41321 AN: 152102 Hom.: 6568 Cov.: 33 AF XY: 0.278 AC XY: 20645 AN XY: 74348

Gnomad4 AFR AF: 0.412

Gnomad4 AMR AF: 0.287

Gnomad4 ASJ AF: 0.224

Gnomad4 EAS AF: 0.485

Gnomad4 SAS AF: 0.290

Gnomad4 FIN AF: 0.243

Gnomad4 NFE AF: 0.175

Gnomad4 OTH AF: 0.237

Alfa AF: 0.227 Hom.: 567

Bravo AF: 0.280

Asia WGS AF: 0.390 AC: 1355 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.21
DANN	Benign	0.27

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: rs37022; hg19: chr5-1415629;