rs3776512

Variant names:

• chr5-1407001-G-A
• rs3776512
• NM_001044.5:c.1499-713C>T

Your query was ambiguous. Multiple possible variants found:

• chr5-1407001-G-A
• chr5-1407001-G-C
• chr5-1407001-G-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.1499-713C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.148 in 152,198 control chromosomes in the GnomAD database, including 1,914 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 0.15 (1914 hom., cov: 33)
• Consequence: SLC6A3 NM_001044.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.443
• Publications: 8 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=-0.9).
• 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.1499-713C>T		intron_variant	Intron 11 of 14	ENST00000270349.12	NP_001035.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC6A3	ENST00000270349.12	c.1499-713C>T		intron_variant	Intron 11 of 14	1	NM_001044.5	ENSP00000270349.9
SLC6A3	ENST00000713696.1	c.1364-713C>T		intron_variant	Intron 10 of 14			ENSP00000519000.1

Frequencies

GnomAD3 genomes AF: 0.148 AC: 22462 AN: 152080 Hom.: 1917 Cov.: 33

Gnomad AFR AF: 0.0694

Gnomad AMI AF: 0.198

Gnomad AMR AF: 0.131

Gnomad ASJ AF: 0.167

Gnomad EAS AF: 0.0822

Gnomad SAS AF: 0.127

Gnomad FIN AF: 0.156

Gnomad MID AF: 0.196

Gnomad NFE AF: 0.202

Gnomad OTH AF: 0.169

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

GnomAD4 genome AF: 0.148 AC: 22461 AN: 152198 Hom.: 1914 Cov.: 33 AF XY: 0.145 AC XY: 10778 AN XY: 74424

African (AFR) AF: 0.0696 AC: 2889 AN: 41528

American (AMR) AF: 0.131 AC: 2006 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.167 AC: 578 AN: 3470

East Asian (EAS) AF: 0.0816 AC: 423 AN: 5184

South Asian (SAS) AF: 0.127 AC: 614 AN: 4824

European-Finnish (FIN) AF: 0.156 AC: 1650 AN: 10590

Middle Eastern (MID) AF: 0.190 AC: 56 AN: 294

European-Non Finnish (NFE) AF: 0.202 AC: 13713 AN: 67990

Other (OTH) AF: 0.166 AC: 351 AN: 2114

Alfa AF: 0.183 Hom.: 10244

Bravo AF: 0.142

Asia WGS AF: 0.0950 AC: 330 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.23
DANN	Benign	0.59
PhyloP100		-0.44
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: rs3776512; hg19: chr5-1407116;