chr5-1419817-C-G

Variant names:

• chr5-1419817-C-G
• rs2975292
• NM_001044.5:c.927+752G>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.927+752G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.529 in 148,102 control chromosomes in the GnomAD database, including 22,099 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 0.53 (22099 hom., cov: 22)
• Consequence: SLC6A3 NM_001044.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.90
• Publications: 13 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=-1.01).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.638 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC6A3	NM_001044.5	c.927+752G>C		intron_variant	Intron 6 of 14	ENST00000270349.12	NP_001035.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC6A3	ENST00000270349.12	c.927+752G>C		intron_variant	Intron 6 of 14	1	NM_001044.5	ENSP00000270349.9
SLC6A3	ENST00000713696.1	c.792+2059G>C		intron_variant	Intron 5 of 14			ENSP00000519000.1
SLC6A3	ENST00000713697.1	n.927+752G>C		intron_variant	Intron 6 of 10			ENSP00000519001.1

Frequencies

GnomAD3 genomes AF: 0.529 AC: 78293 AN: 147988 Hom.: 22082 Cov.: 22

Gnomad AFR AF: 0.389

Gnomad AMI AF: 0.638

Gnomad AMR AF: 0.492

Gnomad ASJ AF: 0.545

Gnomad EAS AF: 0.129

Gnomad SAS AF: 0.485

Gnomad FIN AF: 0.583

Gnomad MID AF: 0.487

Gnomad NFE AF: 0.643

Gnomad OTH AF: 0.544

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

GnomAD4 genome AF: 0.529 AC: 78355 AN: 148102 Hom.: 22099 Cov.: 22 AF XY: 0.525 AC XY: 37819 AN XY: 72062

African (AFR) AF: 0.390 AC: 15580 AN: 39986

American (AMR) AF: 0.491 AC: 7336 AN: 14928

Ashkenazi Jewish (ASJ) AF: 0.545 AC: 1877 AN: 3444

East Asian (EAS) AF: 0.130 AC: 651 AN: 5016

South Asian (SAS) AF: 0.484 AC: 2181 AN: 4502

European-Finnish (FIN) AF: 0.583 AC: 5873 AN: 10082

Middle Eastern (MID) AF: 0.500 AC: 145 AN: 290

European-Non Finnish (NFE) AF: 0.643 AC: 43035 AN: 66928

Other (OTH) AF: 0.545 AC: 1109 AN: 2036

Alfa AF: 0.461 Hom.: 1394

Bravo AF: 0.512

Asia WGS AF: 0.356 AC: 1240 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.41
DANN	Benign	0.51
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: rs2975292; hg19: chr5-1419932;