chr5-1435987-G-A

Variant names:

• chr5-1435987-G-A
• rs9312866
• NM_001044.5:c.419-3289C>T

Variant summary

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

The NM_001044.5(SLC6A3):​c.419-3289C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. 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 0.16 (2655 hom., cov: 19)
• Consequence: SLC6A3 NM_001044.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0560
• Publications: 1 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=-0.84).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.199 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC6A3	NM_001044.5	c.419-3289C>T		intron_variant	Intron 3 of 14	ENST00000270349.12	NP_001035.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC6A3	ENST00000270349.12	c.419-3289C>T		intron_variant	Intron 3 of 14	1	NM_001044.5	ENSP00000270349.9
SLC6A3	ENST00000713696.1	c.419-3289C>T		intron_variant	Intron 3 of 14			ENSP00000519000.1
SLC6A3	ENST00000713698.1	c.419-3289C>T		intron_variant	Intron 3 of 4			ENSP00000519002.1
SLC6A3	ENST00000713697.1	n.419-3289C>T		intron_variant	Intron 3 of 10			ENSP00000519001.1

Frequencies

GnomAD3 genomes AF: 0.163 AC: 21386 AN: 131198 Hom.: 2649 Cov.: 19

Gnomad AFR AF: 0.0877

Gnomad AMI AF: 0.175

Gnomad AMR AF: 0.166

Gnomad ASJ AF: 0.178

Gnomad EAS AF: 0.0804

Gnomad SAS AF: 0.175

Gnomad FIN AF: 0.220

Gnomad MID AF: 0.181

Gnomad NFE AF: 0.202

Gnomad OTH AF: 0.167

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

GnomAD4 genome AF: 0.163 AC: 21413 AN: 131298 Hom.: 2655 Cov.: 19 AF XY: 0.163 AC XY: 10389 AN XY: 63580

African (AFR) AF: 0.0876 AC: 3097 AN: 35362

American (AMR) AF: 0.166 AC: 2172 AN: 13086

Ashkenazi Jewish (ASJ) AF: 0.178 AC: 548 AN: 3078

East Asian (EAS) AF: 0.0804 AC: 345 AN: 4292

South Asian (SAS) AF: 0.178 AC: 646 AN: 3636

European-Finnish (FIN) AF: 0.220 AC: 1853 AN: 8414

Middle Eastern (MID) AF: 0.181 AC: 47 AN: 260

European-Non Finnish (NFE) AF: 0.202 AC: 12254 AN: 60552

Other (OTH) AF: 0.171 AC: 308 AN: 1800

Alfa AF: 0.194 Hom.: 248

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	5.9
DANN	Benign	0.33
PhyloP100		0.056
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: rs9312866; hg19: chr5-1436102;