NM_001044.5:c.418+3300C>T

Variant names:

• chr5-1438059-G-A
• rs1048953
• NM_001044.5:c.418+3300C>T

Variant summary

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

The NM_001044.5(SLC6A3):​c.418+3300C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.271 in 152,154 control chromosomes in the GnomAD database, including 7,275 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 0.27 (7275 hom., cov: 33)
• Consequence: SLC6A3 NM_001044.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.00
• Publications: 9 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=-0.95).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.4 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.418+3300C>T		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.418+3300C>T		intron	N/A	ENSP00000270349.9
	SLC6A3	ENST00000713696.1		c.418+3300C>T		intron	N/A	ENSP00000519000.1
	SLC6A3	ENST00000713698.1		c.418+3300C>T		intron	N/A	ENSP00000519002.1

Frequencies

GnomAD3 genomes AF: 0.271 AC: 41198 AN: 152036 Hom.: 7278 Cov.: 33

Gnomad AFR AF: 0.0741

Gnomad AMI AF: 0.428

Gnomad AMR AF: 0.258

Gnomad ASJ AF: 0.313

Gnomad EAS AF: 0.00944

Gnomad SAS AF: 0.212

Gnomad FIN AF: 0.328

Gnomad MID AF: 0.275

Gnomad NFE AF: 0.404

Gnomad OTH AF: 0.296

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

GnomAD4 genome AF: 0.271 AC: 41183 AN: 152154 Hom.: 7275 Cov.: 33 AF XY: 0.266 AC XY: 19804 AN XY: 74362

African (AFR) AF: 0.0739 AC: 3068 AN: 41538

American (AMR) AF: 0.258 AC: 3941 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.313 AC: 1086 AN: 3472

East Asian (EAS) AF: 0.00946 AC: 49 AN: 5180

South Asian (SAS) AF: 0.211 AC: 1015 AN: 4810

European-Finnish (FIN) AF: 0.328 AC: 3470 AN: 10574

Middle Eastern (MID) AF: 0.282 AC: 83 AN: 294

European-Non Finnish (NFE) AF: 0.404 AC: 27467 AN: 67970

Other (OTH) AF: 0.291 AC: 615 AN: 2112

Alfa AF: 0.366 Hom.: 5056

Bravo AF: 0.256

Asia WGS AF: 0.115 AC: 400 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.29
DANN	Benign	0.72
PhyloP100		-2.0
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: rs1048953; hg19: chr5-1438174;