5-1400730-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_001044.5(SLC6A3):c.1839+185G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0152 in 152,288 control chromosomes in the GnomAD database, including 33 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.015 ( 33 hom., cov: 33)

Consequence

SLC6A3
NM_001044.5 intron

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.182

Publications

1 publications found

Variant links:

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

SLC6A3 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.91).

BP6

Variant 5-1400730-C-T is Benign according to our data. Variant chr5-1400730-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 1207269.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0152 (2321/152288) while in subpopulation NFE AF = 0.0229 (1559/68000). AF 95% confidence interval is 0.022. There are 33 homozygotes in GnomAd4. There are 1056 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 33 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC6A3	NM_001044.5 link	c.1839+185G>A		intron_variant	Intron 14 of 14	ENST00000270349.12	NP_001035.1	Q01959

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
SLC6A3	ENST00000270349.12 link	c.1839+185G>A	intron_variant	Intron 14 of 14	1	NM_001044.5	ENSP00000270349.9	Q01959
SLC6A3	ENST00000512002.2 link	n.220+185G>A	intron_variant	Intron 2 of 2	1
SLC6A3	ENST00000713696.1 link	c.*34+185G>A	intron_variant	Intron 14 of 14			ENSP00000519000.1

Frequencies

GnomAD3 genomes

AF:

0.0152

AC:

2320

AN:

152170

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00488

Gnomad AMI

AF:

0.0252

Gnomad AMR

AF:

0.0157

Gnomad ASJ

AF:

0.0400

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00455

Gnomad FIN

AF:

0.00593

Gnomad MID

AF:

0.0380

Gnomad NFE

AF:

0.0229

Gnomad OTH

AF:

0.0287

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

GnomAD4 genome

AF:

0.0152

AC:

2321

AN:

152288

Hom.:

Cov.:

AF XY:

0.0142

AC XY:

1056

AN XY:

74476

show subpopulations

African (AFR)

AF:

0.00489

AC:

203

AN:

41552

American (AMR)

AF:

0.0158

AC:

242

AN:

15312

Ashkenazi Jewish (ASJ)

AF:

0.0400

AC:

139

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5174

South Asian (SAS)

AF:

0.00435

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00593

AC:

AN:

10628

Middle Eastern (MID)

AF:

0.0374

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0229

AC:

1559

AN:

68000

Other (OTH)

AF:

0.0284

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

111

221

332

442

553

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0186

Hom.:

Bravo

AF:

0.0166

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Oct 02, 2018

GeneDx

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

3.2

(source)

DANN

Benign

0.54

PhyloP100

-0.18

Mutation Taster

=100/0

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

5-1400730-C-T

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over