5-1430719-G-T

Position:

• chr5-1430719-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001044.5(SLC6A3):​c.653+1745C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.307 in 151,390 control chromosomes in the GnomAD database, including 8,003 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 (8003 hom., cov: 31)
• Consequence: SLC6A3 NM_001044.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.29

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• 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/exons	MANE	Protein	UniProt
SLC6A3	NM_001044.5	c.653+1745C>A		intron_variant		ENST00000270349.12	NP_001035.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC6A3	ENST00000270349.12	c.653+1745C>A		intron_variant		1	NM_001044.5	ENSP00000270349.9

Frequencies

GnomAD3 genomes AF: 0.307 AC: 46478 AN: 151270 Hom.: 7997 Cov.: 31

Gnomad AFR AF: 0.427

Gnomad AMI AF: 0.206

Gnomad AMR AF: 0.333

Gnomad ASJ AF: 0.282

Gnomad EAS AF: 0.517

Gnomad SAS AF: 0.423

Gnomad FIN AF: 0.296

Gnomad MID AF: 0.283

Gnomad NFE AF: 0.210

Gnomad OTH AF: 0.280

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

GnomAD4 genome AF: 0.307 AC: 46521 AN: 151390 Hom.: 8003 Cov.: 31 AF XY: 0.315 AC XY: 23271 AN XY: 73938

Gnomad4 AFR AF: 0.427

Gnomad4 AMR AF: 0.333

Gnomad4 ASJ AF: 0.282

Gnomad4 EAS AF: 0.517

Gnomad4 SAS AF: 0.422

Gnomad4 FIN AF: 0.296

Gnomad4 NFE AF: 0.210

Gnomad4 OTH AF: 0.282

Alfa AF: 0.128 Hom.: 198

Bravo AF: 0.311

Asia WGS AF: 0.441 AC: 1533 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.71
DANN	Benign	0.51

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

Publications

LitVar

Other links and lift over

dbSNP: rs409588; hg19: chr5-1430834;