5-1443858-G-T

Variant names:

• chr5-1443858-G-T
• rs2937638
• NM_001044.5:c.-45-616C>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.-45-616C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.3 in 150,910 control chromosomes in the GnomAD database, including 8,559 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 0.30 (8559 hom., cov: 31)
• Consequence: SLC6A3 NM_001044.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.09
• Publications: 2 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=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.506 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC6A3	NM_001044.5	c.-45-616C>A		intron_variant	Intron 1 of 14	ENST00000270349.12	NP_001035.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC6A3	ENST00000270349.12	c.-45-616C>A		intron_variant	Intron 1 of 14	1	NM_001044.5	ENSP00000270349.9
SLC6A3	ENST00000713696.1	c.-45-616C>A		intron_variant	Intron 1 of 14			ENSP00000519000.1
SLC6A3	ENST00000713698.1	c.-45-616C>A		intron_variant	Intron 1 of 4			ENSP00000519002.1
SLC6A3	ENST00000713697.1	n.-45-616C>A		intron_variant	Intron 1 of 10			ENSP00000519001.1

Frequencies

GnomAD3 genomes AF: 0.300 AC: 45219 AN: 150794 Hom.: 8548 Cov.: 31

Gnomad AFR AF: 0.511

Gnomad AMI AF: 0.114

Gnomad AMR AF: 0.323

Gnomad ASJ AF: 0.150

Gnomad EAS AF: 0.453

Gnomad SAS AF: 0.373

Gnomad FIN AF: 0.240

Gnomad MID AF: 0.218

Gnomad NFE AF: 0.170

Gnomad OTH AF: 0.284

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

GnomAD4 genome AF: 0.300 AC: 45256 AN: 150910 Hom.: 8559 Cov.: 31 AF XY: 0.306 AC XY: 22570 AN XY: 73684

African (AFR) AF: 0.511 AC: 21011 AN: 41088

American (AMR) AF: 0.322 AC: 4889 AN: 15172

Ashkenazi Jewish (ASJ) AF: 0.150 AC: 516 AN: 3448

East Asian (EAS) AF: 0.453 AC: 2317 AN: 5120

South Asian (SAS) AF: 0.371 AC: 1772 AN: 4772

European-Finnish (FIN) AF: 0.240 AC: 2497 AN: 10388

Middle Eastern (MID) AF: 0.224 AC: 65 AN: 290

European-Non Finnish (NFE) AF: 0.170 AC: 11494 AN: 67644

Other (OTH) AF: 0.284 AC: 593 AN: 2090

Alfa AF: 0.0839 Hom.: 87

Bravo AF: 0.311

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.13
DANN	Benign	0.28
PhyloP100		-1.1
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: rs2937638; hg19: chr5-1443973;