rs11564775

Positions:

• chr5-1393638-A-G
• chr5-1393638-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.*1097T>C 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 0.070 (18 hom., cov: 0)
  • Exomes 𝑓: 0.030 (0 hom.)
• Consequence: SLC6A3 NM_001044.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.10

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=-1.01).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0975 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC6A3	NM_001044.5	c.*1097T>C		3_prime_UTR_variant	15/15	ENST00000270349.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC6A3	ENST00000270349.12	c.*1097T>C		3_prime_UTR_variant	15/15	1	NM_001044.5	P1

Frequencies

GnomAD3 genomes AF: 0.0697 AC: 3130 AN: 44932 Hom.: 18 Cov.: 0

Gnomad AFR AF: 0.102

Gnomad AMI AF: 0.0929

Gnomad AMR AF: 0.0531

Gnomad ASJ AF: 0.0616

Gnomad EAS AF: 0.0388

Gnomad SAS AF: 0.0521

Gnomad FIN AF: 0.0648

Gnomad MID AF: 0.235

Gnomad NFE AF: 0.0573

Gnomad OTH AF: 0.0753

GnomAD4 exome AF: 0.0297 AC: 29 AN: 978 Hom.: 0 Cov.: 0 AF XY: 0.0331 AC XY: 18 AN XY: 544

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.100

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0309

Gnomad4 OTH exome AF: 0.0517

GnomAD4 genome AF: 0.0697 AC: 3135 AN: 44962 Hom.: 18 Cov.: 0 AF XY: 0.0686 AC XY: 1538 AN XY: 22416

Gnomad4 AFR AF: 0.102

Gnomad4 AMR AF: 0.0534

Gnomad4 ASJ AF: 0.0616

Gnomad4 EAS AF: 0.0390

Gnomad4 SAS AF: 0.0536

Gnomad4 FIN AF: 0.0648

Gnomad4 NFE AF: 0.0573

Gnomad4 OTH AF: 0.0759

Alfa AF: 0.338 Hom.: 363

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	2.0
DANN	Benign	0.068

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: rs11564775; hg19: chr5-1393753;