rs2550936

chr5-1411141-A-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001044.5(SLC6A3):c.1269+102T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.284 in 810,430 control chromosomes in the GnomAD database, including 38,938 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.37 (13247 hom., cov: 32)
  • Exomes 𝑓: 0.26 (25691 hom.)
• Consequence: SLC6A3 NM_001044.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.08

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 5-1411141-A-C is Benign according to our data. Variant chr5-1411141-A-C is described in ClinVar as [Benign]. Clinvar id is 1180279.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.671 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC6A3	NM_001044.5	c.1269+102T>G		intron_variant		ENST00000270349.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC6A3	ENST00000270349.12	c.1269+102T>G		intron_variant		1	NM_001044.5	P1

Frequencies

GnomAD3 genomes AF: 0.370 AC: 56111 AN: 151852 Hom.: 13208 Cov.: 32

Gnomad AFR AF: 0.677

Gnomad AMI AF: 0.311

Gnomad AMR AF: 0.225

Gnomad ASJ AF: 0.277

Gnomad EAS AF: 0.117

Gnomad SAS AF: 0.247

Gnomad FIN AF: 0.235

Gnomad MID AF: 0.306

Gnomad NFE AF: 0.270

Gnomad OTH AF: 0.327

GnomAD4 exome AF: 0.265 AC: 174172 AN: 658460 Hom.: 25691 AF XY: 0.262 AC XY: 91435 AN XY: 349108

Gnomad4 AFR exome AF: 0.685

Gnomad4 AMR exome AF: 0.166

Gnomad4 ASJ exome AF: 0.283

Gnomad4 EAS exome AF: 0.101

Gnomad4 SAS exome AF: 0.236

Gnomad4 FIN exome AF: 0.241

Gnomad4 NFE exome AF: 0.272

Gnomad4 OTH exome AF: 0.284

GnomAD4 genome AF: 0.370 AC: 56201 AN: 151970 Hom.: 13247 Cov.: 32 AF XY: 0.361 AC XY: 26800 AN XY: 74274

Gnomad4 AFR AF: 0.678

Gnomad4 AMR AF: 0.225

Gnomad4 ASJ AF: 0.277

Gnomad4 EAS AF: 0.117

Gnomad4 SAS AF: 0.248

Gnomad4 FIN AF: 0.235

Gnomad4 NFE AF: 0.270

Gnomad4 OTH AF: 0.322

Alfa AF: 0.331 Hom.: 1277

Bravo AF: 0.382

Asia WGS AF: 0.205 AC: 714 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

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	-0.90
Cadd	Benign	0.083
Dann	Benign	0.43

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: rs2550936; hg19: chr5-1411256;