chr5-1412530-C-T

Variant names:

• chr5-1412530-C-T
• rs27048
• NM_001044.5:c.1157-1175G>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.1157-1175G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.398 in 152,156 control chromosomes in the GnomAD database, including 12,511 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 0.40 (12511 hom., cov: 34)
• Consequence: SLC6A3 NM_001044.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.54
• Publications: 34 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.441 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.1157-1175G>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.1157-1175G>A		intron	N/A	ENSP00000270349.9	Q01959
	SLC6A3	ENST00000941790.1		c.1022-1175G>A		intron	N/A	ENSP00000611849.1
	SLC6A3	ENST00000713696.1		c.1022-1175G>A		intron	N/A	ENSP00000519000.1	A0AAQ5BGN6

Frequencies

GnomAD3 genomes AF: 0.398 AC: 60495 AN: 152038 Hom.: 12504 Cov.: 34

Gnomad AFR AF: 0.355

Gnomad AMI AF: 0.443

Gnomad AMR AF: 0.328

Gnomad ASJ AF: 0.489

Gnomad EAS AF: 0.167

Gnomad SAS AF: 0.362

Gnomad FIN AF: 0.458

Gnomad MID AF: 0.453

Gnomad NFE AF: 0.445

Gnomad OTH AF: 0.391

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

GnomAD4 genome AF: 0.398 AC: 60542 AN: 152156 Hom.: 12511 Cov.: 34 AF XY: 0.394 AC XY: 29302 AN XY: 74376

African (AFR) AF: 0.355 AC: 14727 AN: 41518

American (AMR) AF: 0.328 AC: 5015 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.489 AC: 1698 AN: 3470

East Asian (EAS) AF: 0.168 AC: 871 AN: 5184

South Asian (SAS) AF: 0.361 AC: 1738 AN: 4820

European-Finnish (FIN) AF: 0.458 AC: 4846 AN: 10586

Middle Eastern (MID) AF: 0.452 AC: 133 AN: 294

European-Non Finnish (NFE) AF: 0.445 AC: 30282 AN: 67984

Other (OTH) AF: 0.393 AC: 828 AN: 2108

Alfa AF: 0.423 Hom.: 30851

Bravo AF: 0.385

Asia WGS AF: 0.305 AC: 1058 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.86
DANN	Benign	0.62
PhyloP100		-2.5
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: rs27048; hg19: chr5-1412645;