5-1401465-C-T

Variant names:

• chr5-1401465-C-T
• rs11133767
• NM_001044.5:c.1768-479G>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.1768-479G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.351 in 152,162 control chromosomes in the GnomAD database, including 10,241 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 0.35 (10241 hom., cov: 33)
• Consequence: SLC6A3 NM_001044.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.286
• Publications: 17 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=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.498 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.1768-479G>A		intron	N/A	NP_001035.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC6A3	ENST00000270349.12	TSL:1 MANE Select	c.1768-479G>A		intron	N/A	ENSP00000270349.9
	SLC6A3	ENST00000941790.1		c.1633-479G>A		intron	N/A	ENSP00000611849.1
	SLC6A3	ENST00000713696.1		c.1682-479G>A		intron	N/A	ENSP00000519000.1

Frequencies

GnomAD3 genomes AF: 0.351 AC: 53383 AN: 152044 Hom.: 10217 Cov.: 33

Gnomad AFR AF: 0.503

Gnomad AMI AF: 0.344

Gnomad AMR AF: 0.256

Gnomad ASJ AF: 0.360

Gnomad EAS AF: 0.105

Gnomad SAS AF: 0.236

Gnomad FIN AF: 0.260

Gnomad MID AF: 0.424

Gnomad NFE AF: 0.321

Gnomad OTH AF: 0.346

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

GnomAD4 genome AF: 0.351 AC: 53451 AN: 152162 Hom.: 10241 Cov.: 33 AF XY: 0.343 AC XY: 25494 AN XY: 74388

African (AFR) AF: 0.504 AC: 20901 AN: 41510

American (AMR) AF: 0.255 AC: 3905 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.360 AC: 1249 AN: 3468

East Asian (EAS) AF: 0.104 AC: 541 AN: 5178

South Asian (SAS) AF: 0.237 AC: 1139 AN: 4816

European-Finnish (FIN) AF: 0.260 AC: 2755 AN: 10594

Middle Eastern (MID) AF: 0.435 AC: 128 AN: 294

European-Non Finnish (NFE) AF: 0.321 AC: 21799 AN: 67988

Other (OTH) AF: 0.342 AC: 721 AN: 2110

Alfa AF: 0.324 Hom.: 4814

Bravo AF: 0.357

Asia WGS AF: 0.189 AC: 660 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.41
DANN	Benign	0.59
PhyloP100		-0.29
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: rs11133767; hg19: chr5-1401580;