rs1042098

chr5-1394700-A-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001044.5(SLC6A3):c.*35T>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 0.261 in 1,607,322 control chromosomes in the GnomAD database, including 58,493 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.31 (7814 hom., cov: 33)
  • Exomes 𝑓: 0.26 (50679 hom.)
• Consequence: SLC6A3 NM_001044.5 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.652

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 5-1394700-A-G is Benign according to our data. Variant chr5-1394700-A-G is described in ClinVar as [Benign]. Clinvar id is 1288828.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.447 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC6A3	NM_001044.5	c.*35T>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.*35T>C		3_prime_UTR_variant	15/15	1	NM_001044.5	P1
SLC6A3	ENST00000512002.2	n.279T>C		non_coding_transcript_exon_variant	3/3	1

Frequencies

GnomAD3 genomes AF: 0.305 AC: 46431 AN: 152022 Hom.: 7795 Cov.: 33

Gnomad AFR AF: 0.452

Gnomad AMI AF: 0.212

Gnomad AMR AF: 0.243

Gnomad ASJ AF: 0.414

Gnomad EAS AF: 0.101

Gnomad SAS AF: 0.236

Gnomad FIN AF: 0.189

Gnomad MID AF: 0.424

Gnomad NFE AF: 0.264

Gnomad OTH AF: 0.312

GnomAD3 exomes AF: 0.249 AC: 62568 AN: 251402 Hom.: 8896 AF XY: 0.250 AC XY: 33903 AN XY: 135866

Gnomad AFR exome AF: 0.460

Gnomad AMR exome AF: 0.170

Gnomad ASJ exome AF: 0.424

Gnomad EAS exome AF: 0.0967

Gnomad SAS exome AF: 0.228

Gnomad FIN exome AF: 0.188

Gnomad NFE exome AF: 0.267

Gnomad OTH exome AF: 0.291

GnomAD4 exome AF: 0.257 AC: 373267 AN: 1455182 Hom.: 50679 Cov.: 29 AF XY: 0.256 AC XY: 185585 AN XY: 724410

Gnomad4 AFR exome AF: 0.464

Gnomad4 AMR exome AF: 0.178

Gnomad4 ASJ exome AF: 0.416

Gnomad4 EAS exome AF: 0.0880

Gnomad4 SAS exome AF: 0.228

Gnomad4 FIN exome AF: 0.196

Gnomad4 NFE exome AF: 0.259

Gnomad4 OTH exome AF: 0.283

GnomAD4 genome AF: 0.306 AC: 46499 AN: 152140 Hom.: 7814 Cov.: 33 AF XY: 0.299 AC XY: 22241 AN XY: 74380

Gnomad4 AFR AF: 0.453

Gnomad4 AMR AF: 0.243

Gnomad4 ASJ AF: 0.414

Gnomad4 EAS AF: 0.101

Gnomad4 SAS AF: 0.236

Gnomad4 FIN AF: 0.189

Gnomad4 NFE AF: 0.264

Gnomad4 OTH AF: 0.309

Alfa AF: 0.279 Hom.: 11137

Bravo AF: 0.317

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Classic dopamine transporter deficiency syndrome Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 15, 2021

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 05, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	2.2
Dann	Benign	0.34

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: rs1042098; hg19: chr5-1394815; COSMIC: COSV54361722;