NM_001044.5:c.1032-474G>C

Variant names:

• chr5-1415289-C-G
• rs466630
• NM_001044.5:c.1032-474G>C

Variant summary

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

The NM_001044.5(SLC6A3):​c.1032-474G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.71 in 151,560 control chromosomes in the GnomAD database, including 38,680 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 0.71 (38680 hom., cov: 32)
• Consequence: SLC6A3 NM_001044.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.85
• 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), 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=-0.96).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.736 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC6A3	NM_001044.5	c.1032-474G>C		intron_variant	Intron 7 of 14	ENST00000270349.12	NP_001035.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC6A3	ENST00000270349.12	c.1032-474G>C		intron_variant	Intron 7 of 14	1	NM_001044.5	ENSP00000270349.9
SLC6A3	ENST00000713696.1	c.897-474G>C		intron_variant	Intron 6 of 14			ENSP00000519000.1
SLC6A3	ENST00000511750.1	n.482-474G>C		intron_variant	Intron 1 of 1	4
SLC6A3	ENST00000713697.1	n.1032-29G>C		intron_variant	Intron 7 of 10			ENSP00000519001.1

Frequencies

GnomAD3 genomes AF: 0.710 AC: 107463 AN: 151440 Hom.: 38637 Cov.: 32

Gnomad AFR AF: 0.736

Gnomad AMI AF: 0.827

Gnomad AMR AF: 0.597

Gnomad ASJ AF: 0.867

Gnomad EAS AF: 0.492

Gnomad SAS AF: 0.702

Gnomad FIN AF: 0.604

Gnomad MID AF: 0.842

Gnomad NFE AF: 0.742

Gnomad OTH AF: 0.732

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

GnomAD4 genome AF: 0.710 AC: 107566 AN: 151560 Hom.: 38680 Cov.: 32 AF XY: 0.701 AC XY: 51912 AN XY: 74060

African (AFR) AF: 0.736 AC: 30399 AN: 41308

American (AMR) AF: 0.597 AC: 9115 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.867 AC: 3003 AN: 3464

East Asian (EAS) AF: 0.492 AC: 2523 AN: 5126

South Asian (SAS) AF: 0.702 AC: 3370 AN: 4800

European-Finnish (FIN) AF: 0.604 AC: 6349 AN: 10512

Middle Eastern (MID) AF: 0.850 AC: 250 AN: 294

European-Non Finnish (NFE) AF: 0.742 AC: 50270 AN: 67776

Other (OTH) AF: 0.732 AC: 1543 AN: 2108

Alfa AF: 0.603 Hom.: 1641

Bravo AF: 0.711

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.028
DANN	Benign	0.33
PhyloP100		-1.9
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: rs466630; hg19: chr5-1415404;