ENST00000512002.2:n.494G>C

Variant names:

• chr5-1394485-C-G
• rs11564774
• ENST00000512002.2:n.494G>C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000512002.2(SLC6A3):​n.494G>C variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.223 in 610,794 control chromosomes in the GnomAD database, including 16,174 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.24 (4474 hom., cov: 33)
  • Exomes 𝑓: 0.22 (11700 hom.)
• Consequence: SLC6A3 ENST00000512002.2 non_coding_transcript_exon
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.552
• Publications: 19 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BP6: Variant 5-1394485-C-G is Benign according to our data. Variant chr5-1394485-C-G is described in ClinVar as Benign. ClinVar VariationId is 1259994.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.287 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000512002.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC6A3	NM_001044.5	MANE Select	c.*250G>C		3_prime_UTR	Exon 15 of 15	NP_001035.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC6A3	ENST00000512002.2	TSL:1	n.494G>C		non_coding_transcript_exon	Exon 3 of 3
	SLC6A3	ENST00000270349.12	TSL:1 MANE Select	c.*250G>C		3_prime_UTR	Exon 15 of 15	ENSP00000270349.9
	SLC6A3	ENST00000713696.1		c.*308G>C		3_prime_UTR	Exon 15 of 15	ENSP00000519000.1

Frequencies

GnomAD3 genomes AF: 0.240 AC: 36412 AN: 152012 Hom.: 4464 Cov.: 33

Gnomad AFR AF: 0.291

Gnomad AMI AF: 0.204

Gnomad AMR AF: 0.208

Gnomad ASJ AF: 0.272

Gnomad EAS AF: 0.0921

Gnomad SAS AF: 0.223

Gnomad FIN AF: 0.173

Gnomad MID AF: 0.358

Gnomad NFE AF: 0.236

Gnomad OTH AF: 0.260

GnomAD4 exome AF: 0.218 AC: 99808 AN: 458664 Hom.: 11700 Cov.: 3 AF XY: 0.217 AC XY: 52545 AN XY: 242270

African (AFR) AF: 0.297 AC: 3829 AN: 12910

American (AMR) AF: 0.157 AC: 3845 AN: 24422

Ashkenazi Jewish (ASJ) AF: 0.270 AC: 3906 AN: 14472

East Asian (EAS) AF: 0.0802 AC: 2478 AN: 30886

South Asian (SAS) AF: 0.214 AC: 10112 AN: 47166

European-Finnish (FIN) AF: 0.181 AC: 5277 AN: 29188

Middle Eastern (MID) AF: 0.319 AC: 903 AN: 2834

European-Non Finnish (NFE) AF: 0.234 AC: 63179 AN: 270516

Other (OTH) AF: 0.239 AC: 6279 AN: 26270

GnomAD4 genome AF: 0.240 AC: 36455 AN: 152130 Hom.: 4474 Cov.: 33 AF XY: 0.237 AC XY: 17594 AN XY: 74378

African (AFR) AF: 0.292 AC: 12098 AN: 41484

American (AMR) AF: 0.208 AC: 3179 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.272 AC: 945 AN: 3472

East Asian (EAS) AF: 0.0918 AC: 475 AN: 5176

South Asian (SAS) AF: 0.223 AC: 1077 AN: 4830

European-Finnish (FIN) AF: 0.173 AC: 1828 AN: 10582

Middle Eastern (MID) AF: 0.367 AC: 108 AN: 294

European-Non Finnish (NFE) AF: 0.236 AC: 16019 AN: 67970

Other (OTH) AF: 0.256 AC: 540 AN: 2108

Alfa AF: 0.230 Hom.: 555

Bravo AF: 0.246

Asia WGS AF: 0.161 AC: 561 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

Jul 05, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	2.3
DANN	Benign	0.35
PhyloP100		0.55
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: rs11564774; hg19: chr5-1394600;