5-1392948-A-G

Position:

• chr5-1392948-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.*1787T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.21 in 151,396 control chromosomes in the GnomAD database, including 3,639 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 (3635 hom., cov: 32)
  • Exomes 𝑓: 0.29 (4 hom.)
• Consequence: SLC6A3 NM_001044.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0850

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 (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.*1787T>C		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.*1787T>C		3_prime_UTR_variant	15/15	1	NM_001044.5	ENSP00000270349.9

Frequencies

GnomAD3 genomes AF: 0.210 AC: 31789 AN: 151206 Hom.: 3636 Cov.: 32

Gnomad AFR AF: 0.138

Gnomad AMI AF: 0.211

Gnomad AMR AF: 0.206

Gnomad ASJ AF: 0.399

Gnomad EAS AF: 0.0668

Gnomad SAS AF: 0.167

Gnomad FIN AF: 0.185

Gnomad MID AF: 0.385

Gnomad NFE AF: 0.261

Gnomad OTH AF: 0.254

GnomAD4 exome AF: 0.294 AC: 20 AN: 68 Hom.: 4 Cov.: 0 AF XY: 0.333 AC XY: 14 AN XY: 42

Gnomad4 AFR exome AF: 0.00

Gnomad4 ASJ exome AF: 1.00

Gnomad4 SAS exome AF: 0.500

Gnomad4 FIN exome AF: 0.250

Gnomad4 NFE exome AF: 0.304

Gnomad4 OTH exome AF: 0.125

GnomAD4 genome AF: 0.210 AC: 31788 AN: 151328 Hom.: 3635 Cov.: 32 AF XY: 0.206 AC XY: 15236 AN XY: 73990

Gnomad4 AFR AF: 0.138

Gnomad4 AMR AF: 0.206

Gnomad4 ASJ AF: 0.399

Gnomad4 EAS AF: 0.0664

Gnomad4 SAS AF: 0.166

Gnomad4 FIN AF: 0.185

Gnomad4 NFE AF: 0.261

Gnomad4 OTH AF: 0.250

Alfa AF: 0.222 Hom.: 1002

Bravo AF: 0.211

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	4.9
DANN	Benign	0.17

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: rs1809939; hg19: chr5-1393063;