rs6876890

Positions:

• chr5-1393763-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.*972C>T variant causes a 3 prime UTR 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 0.21 (3187 hom., cov: 19)
  • Exomes 𝑓: 0.19 (48 hom.)
• Consequence: SLC6A3 NM_001044.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.94

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=-1.0).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.223 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC6A3	NM_001044.5	c.*972C>T		3_prime_UTR_variant	15/15	ENST00000270349.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC6A3	ENST00000270349.12	c.*972C>T		3_prime_UTR_variant	15/15	1	NM_001044.5	P1

Frequencies

GnomAD3 genomes AF: 0.207 AC: 25423 AN: 122792 Hom.: 3177 Cov.: 19

Gnomad AFR AF: 0.200

Gnomad AMI AF: 0.157

Gnomad AMR AF: 0.182

Gnomad ASJ AF: 0.377

Gnomad EAS AF: 0.0782

Gnomad SAS AF: 0.185

Gnomad FIN AF: 0.144

Gnomad MID AF: 0.342

Gnomad NFE AF: 0.227

Gnomad OTH AF: 0.233

GnomAD4 exome AF: 0.189 AC: 278 AN: 1468 Hom.: 48 Cov.: 0 AF XY: 0.179 AC XY: 158 AN XY: 882

Gnomad4 AFR exome AF: 0.313

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.188

Gnomad4 FIN exome AF: 0.223

Gnomad4 NFE exome AF: 0.0659

Gnomad4 OTH exome AF: 0.211

GnomAD4 genome AF: 0.207 AC: 25449 AN: 122868 Hom.: 3187 Cov.: 19 AF XY: 0.203 AC XY: 12009 AN XY: 59160

Gnomad4 AFR AF: 0.200

Gnomad4 AMR AF: 0.182

Gnomad4 ASJ AF: 0.377

Gnomad4 EAS AF: 0.0777

Gnomad4 SAS AF: 0.184

Gnomad4 FIN AF: 0.144

Gnomad4 NFE AF: 0.227

Gnomad4 OTH AF: 0.231

Alfa AF: 0.248 Hom.: 362

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	5.4
DANN	Benign	0.29

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: rs6876890; hg19: chr5-1393878; COSMIC: COSV54368884; COSMIC: COSV54368884;