5-1393229-C-T

Position:

• chr5-1393229-C-T

Variant summary

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

The NM_001044.5(SLC6A3):​c.*1506G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.215 in 152,234 control chromosomes in the GnomAD database, including 3,797 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 (3796 hom., cov: 33)
  • Exomes 𝑓: 0.27 (1 hom.)
• Consequence: SLC6A3 NM_001044.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.668

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=-0.86).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.257 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC6A3	NM_001044.5	c.*1506G>A		3_prime_UTR_variant	15/15	ENST00000270349.12	NP_001035.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC6A3	ENST00000270349	c.*1506G>A		3_prime_UTR_variant	15/15	1	NM_001044.5	ENSP00000270349.9

Frequencies

GnomAD3 genomes AF: 0.215 AC: 32738 AN: 152090 Hom.: 3797 Cov.: 33

Gnomad AFR AF: 0.156

Gnomad AMI AF: 0.212

Gnomad AMR AF: 0.210

Gnomad ASJ AF: 0.399

Gnomad EAS AF: 0.0663

Gnomad SAS AF: 0.167

Gnomad FIN AF: 0.186

Gnomad MID AF: 0.386

Gnomad NFE AF: 0.261

Gnomad OTH AF: 0.261

GnomAD4 exome AF: 0.269 AC: 7 AN: 26 Hom.: 1 Cov.: 0 AF XY: 0.278 AC XY: 5 AN XY: 18

Gnomad4 FIN exome AF: 0.250

Gnomad4 NFE exome AF: 0.300

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.215 AC: 32743 AN: 152208 Hom.: 3796 Cov.: 33 AF XY: 0.211 AC XY: 15718 AN XY: 74430

Gnomad4 AFR AF: 0.156

Gnomad4 AMR AF: 0.210

Gnomad4 ASJ AF: 0.399

Gnomad4 EAS AF: 0.0659

Gnomad4 SAS AF: 0.166

Gnomad4 FIN AF: 0.186

Gnomad4 NFE AF: 0.261

Gnomad4 OTH AF: 0.257

Alfa AF: 0.222 Hom.: 1344

Bravo AF: 0.217

Asia WGS AF: 0.117 AC: 408 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.76
DANN	Benign	0.38

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: rs3797200; hg19: chr5-1393344;