chr5-1431049-G-C

Variant names:

• chr5-1431049-G-C
• rs463379
• NM_001044.5:c.653+1415C>G

Variant summary

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

The NM_001044.5(SLC6A3):​c.653+1415C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.311 in 151,978 control chromosomes in the GnomAD database, including 8,310 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 0.31 (8310 hom., cov: 34)
• Consequence: SLC6A3 NM_001044.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.825
• Publications: 20 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=-0.94).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.501 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC6A3	NM_001044.5	c.653+1415C>G		intron_variant	Intron 4 of 14	ENST00000270349.12	NP_001035.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC6A3	ENST00000270349.12	c.653+1415C>G		intron_variant	Intron 4 of 14	1	NM_001044.5	ENSP00000270349.9
SLC6A3	ENST00000713696.1	c.653+1415C>G		intron_variant	Intron 4 of 14			ENSP00000519000.1
SLC6A3	ENST00000713698.1	c.653+1415C>G		intron_variant	Intron 4 of 4			ENSP00000519002.1
SLC6A3	ENST00000713697.1	n.653+1415C>G		intron_variant	Intron 4 of 10			ENSP00000519001.1

Frequencies

GnomAD3 genomes AF: 0.311 AC: 47287 AN: 151860 Hom.: 8300 Cov.: 34

Gnomad AFR AF: 0.442

Gnomad AMI AF: 0.204

Gnomad AMR AF: 0.334

Gnomad ASJ AF: 0.282

Gnomad EAS AF: 0.517

Gnomad SAS AF: 0.422

Gnomad FIN AF: 0.295

Gnomad MID AF: 0.282

Gnomad NFE AF: 0.210

Gnomad OTH AF: 0.282

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

GnomAD4 genome AF: 0.311 AC: 47338 AN: 151978 Hom.: 8310 Cov.: 34 AF XY: 0.319 AC XY: 23656 AN XY: 74254

African (AFR) AF: 0.442 AC: 18330 AN: 41500

American (AMR) AF: 0.334 AC: 5101 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.282 AC: 977 AN: 3470

East Asian (EAS) AF: 0.517 AC: 2676 AN: 5172

South Asian (SAS) AF: 0.421 AC: 2024 AN: 4804

European-Finnish (FIN) AF: 0.295 AC: 3103 AN: 10524

Middle Eastern (MID) AF: 0.269 AC: 79 AN: 294

European-Non Finnish (NFE) AF: 0.210 AC: 14265 AN: 67932

Other (OTH) AF: 0.283 AC: 597 AN: 2108

Alfa AF: 0.151 Hom.: 273

Bravo AF: 0.317

Asia WGS AF: 0.444 AC: 1545 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.45
DANN	Benign	0.37
PhyloP100		-0.82
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: rs463379; hg19: chr5-1431164;