5-1428399-G-T

Variant names:

• chr5-1428399-G-T
• rs393795
• NM_001044.5:c.653+4065C>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001044.5(SLC6A3):​c.653+4065C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.28 in 151,932 control chromosomes in the GnomAD database, including 6,400 homozygotes. 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 0.28 (6400 hom., cov: 32)
• Consequence: SLC6A3 NM_001044.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0630
• Publications: 29 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), Ambry Genetics, G2P
• 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.501 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC6A3	NM_001044.5	MANE Select	c.653+4065C>A		intron	N/A	NP_001035.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC6A3	ENST00000270349.12	TSL:1 MANE Select	c.653+4065C>A		intron	N/A	ENSP00000270349.9
	SLC6A3	ENST00000713696.1		c.653+4065C>A		intron	N/A	ENSP00000519000.1
	SLC6A3	ENST00000713697.1		n.653+4065C>A		intron	N/A	ENSP00000519001.1

Frequencies

GnomAD3 genomes AF: 0.280 AC: 42463 AN: 151810 Hom.: 6401 Cov.: 32

Gnomad AFR AF: 0.337

Gnomad AMI AF: 0.204

Gnomad AMR AF: 0.323

Gnomad ASJ AF: 0.281

Gnomad EAS AF: 0.517

Gnomad SAS AF: 0.378

Gnomad FIN AF: 0.295

Gnomad MID AF: 0.283

Gnomad NFE AF: 0.209

Gnomad OTH AF: 0.261

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

GnomAD4 genome AF: 0.280 AC: 42491 AN: 151932 Hom.: 6400 Cov.: 32 AF XY: 0.287 AC XY: 21292 AN XY: 74264

African (AFR) AF: 0.336 AC: 13933 AN: 41406

American (AMR) AF: 0.323 AC: 4939 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.281 AC: 974 AN: 3462

East Asian (EAS) AF: 0.518 AC: 2677 AN: 5172

South Asian (SAS) AF: 0.377 AC: 1817 AN: 4816

European-Finnish (FIN) AF: 0.295 AC: 3106 AN: 10536

Middle Eastern (MID) AF: 0.271 AC: 79 AN: 292

European-Non Finnish (NFE) AF: 0.209 AC: 14231 AN: 67952

Other (OTH) AF: 0.262 AC: 550 AN: 2102

Alfa AF: 0.231 Hom.: 2429

Bravo AF: 0.282

Asia WGS AF: 0.414 AC: 1439 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.0
DANN	Benign	0.39
PhyloP100		-0.063
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: rs393795; hg19: chr5-1428514;