NM_001044.5:c.286+185G>A

Variant names:

• chr5-1442727-C-T
• rs13189021
• NM_001044.5:c.286+185G>A

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001044.5(SLC6A3):​c.286+185G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.16 in 152,014 control chromosomes in the GnomAD database, including 2,632 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.16 (2632 hom., cov: 31)
• Consequence: SLC6A3 NM_001044.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.498
• Publications: 4 publications found

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]

SLC6A3 Gene-Disease associations (from GenCC):

• classic dopamine transporter deficiency syndrome

  Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), G2P, PanelApp Australia, Ambry Genetics
• SLC6A3-related dopamine transporter deficiency syndrome

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• parkinsonism-dystonia, infantile

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BP6: Variant 5-1442727-C-T is Benign according to our data. Variant chr5-1442727-C-T is described in ClinVar as Benign. ClinVar VariationId is 1290475.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.221 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001044.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC6A3	NM_001044.5	MANE Select	c.286+185G>A		intron	N/A	NP_001035.1	Q01959

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC6A3	ENST00000270349.12	TSL:1 MANE Select	c.286+185G>A		intron	N/A	ENSP00000270349.9	Q01959
	SLC6A3	ENST00000941790.1		c.286+185G>A		intron	N/A	ENSP00000611849.1
	SLC6A3	ENST00000713696.1		c.286+185G>A		intron	N/A	ENSP00000519000.1	A0AAQ5BGN6

Frequencies

GnomAD3 genomes AF: 0.160 AC: 24284 AN: 151896 Hom.: 2635 Cov.: 31

Gnomad AFR AF: 0.0393

Gnomad AMI AF: 0.218

Gnomad AMR AF: 0.147

Gnomad ASJ AF: 0.315

Gnomad EAS AF: 0.00174

Gnomad SAS AF: 0.112

Gnomad FIN AF: 0.281

Gnomad MID AF: 0.206

Gnomad NFE AF: 0.224

Gnomad OTH AF: 0.167

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.160 AC: 24274 AN: 152014 Hom.: 2632 Cov.: 31 AF XY: 0.161 AC XY: 11980 AN XY: 74290

African (AFR) AF: 0.0393 AC: 1630 AN: 41522

American (AMR) AF: 0.147 AC: 2240 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.315 AC: 1093 AN: 3466

East Asian (EAS) AF: 0.00174 AC: 9 AN: 5162

South Asian (SAS) AF: 0.111 AC: 534 AN: 4806

European-Finnish (FIN) AF: 0.281 AC: 2960 AN: 10540

Middle Eastern (MID) AF: 0.201 AC: 59 AN: 294

European-Non Finnish (NFE) AF: 0.224 AC: 15204 AN: 67934

Other (OTH) AF: 0.165 AC: 346 AN: 2102

Alfa AF: 0.182 Hom.: 2490

Bravo AF: 0.145

Asia WGS AF: 0.0640 AC: 221 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.14
DANN	Benign	0.56
PhyloP100		-0.50
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs13189021; hg19: chr5-1442842;