Variant 5-1394700-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001044.5(SLC6A3):c.*35T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.261 in 1,607,322 control chromosomes in the GnomAD database, including 58,493 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.31 ( 7814 hom., cov: 33)

Exomes 𝑓: 0.26 ( 50679 hom. )

Consequence

SLC6A3
NM_001044.5 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.652

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.89).

BP6

Variant 5-1394700-A-G is Benign according to our data. Variant chr5-1394700-A-G is described in ClinVar as [Benign]. Clinvar id is 1288828.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.447 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC6A3	NM_001044.5 linkuse as main transcript	c.*35T>C		3_prime_UTR_variant	15/15	ENST00000270349.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC6A3	ENST00000270349.12 linkuse as main transcript	c.*35T>C		3_prime_UTR_variant	15/15	1	NM_001044.5	P1
SLC6A3	ENST00000512002.2 linkuse as main transcript	n.279T>C		non_coding_transcript_exon_variant	3/3	1

Frequencies

GnomAD3 genomes

AF:

0.305

AC:

46431

AN:

152022

Hom.:

7795

Cov.:

show subpopulations

Gnomad AFR

AF:

0.452

Gnomad AMI

AF:

0.212

Gnomad AMR

AF:

0.243

Gnomad ASJ

AF:

0.414

Gnomad EAS

AF:

0.101

Gnomad SAS

AF:

0.236

Gnomad FIN

AF:

0.189

Gnomad MID

AF:

0.424

Gnomad NFE

AF:

0.264

Gnomad OTH

AF:

0.312

GnomAD3 exomes

AF:

0.249

AC:

62568

AN:

251402

Hom.:

8896

AF XY:

0.250

AC XY:

33903

AN XY:

135866

show subpopulations

Gnomad AFR exome

AF:

0.460

Gnomad AMR exome

AF:

0.170

Gnomad ASJ exome

AF:

0.424

Gnomad EAS exome

AF:

0.0967

Gnomad SAS exome

AF:

0.228

Gnomad FIN exome

AF:

0.188

Gnomad NFE exome

AF:

0.267

Gnomad OTH exome

AF:

0.291

GnomAD4 exome

AF:

0.257

AC:

373267

AN:

1455182

Hom.:

50679

Cov.:

AF XY:

0.256

AC XY:

185585

AN XY:

724410

show subpopulations

Gnomad4 AFR exome

AF:

0.464

Gnomad4 AMR exome

AF:

0.178

Gnomad4 ASJ exome

AF:

0.416

Gnomad4 EAS exome

AF:

0.0880

Gnomad4 SAS exome

AF:

0.228

Gnomad4 FIN exome

AF:

0.196

Gnomad4 NFE exome

AF:

0.259

Gnomad4 OTH exome

AF:

0.283

GnomAD4 genome

AF:

0.306

AC:

46499

AN:

152140

Hom.:

7814

Cov.:

AF XY:

0.299

AC XY:

22241

AN XY:

74380

show subpopulations

Gnomad4 AFR

AF:

0.453

Gnomad4 AMR

AF:

0.243

Gnomad4 ASJ

AF:

0.414

Gnomad4 EAS

AF:

0.101

Gnomad4 SAS

AF:

0.236

Gnomad4 FIN

AF:

0.189

Gnomad4 NFE

AF:

0.264

Gnomad4 OTH

AF:

0.309

Alfa

AF:

0.279

Hom.:

11137

Bravo

AF:

0.317

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 05, 2018	- -

Classic dopamine transporter deficiency syndrome

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 15, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

2.2

DANN

Benign

0.34

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over