Variant 5-1394545-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_001044.5(SLC6A3):c.*190C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00625 in 703,522 control chromosomes in the GnomAD database, including 56 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0097 ( 25 hom., cov: 33)

Exomes 𝑓: 0.0053 ( 31 hom. )

Consequence

SLC6A3
NM_001044.5 3_prime_UTR

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.0280

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=-0.84).

BP6

Variant 5-1394545-G-A is Benign according to our data. Variant chr5-1394545-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 1197770.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00969 (1476/152344) while in subpopulation AFR AF= 0.0259 (1076/41572). AF 95% confidence interval is 0.0246. There are 25 homozygotes in gnomad4. There are 763 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 25 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC6A3	NM_001044.5 link	c.*190C>T		3_prime_UTR_variant	15/15	ENST00000270349.12	NP_001035.1	Q01959

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC6A3	ENST00000270349 link	c.*190C>T		3_prime_UTR_variant	15/15	1	NM_001044.5	ENSP00000270349.9		Q01959
SLC6A3	ENST00000512002.2 link	n.434C>T		non_coding_transcript_exon_variant	3/3	1

Frequencies

GnomAD3 genomes

AF:

0.00961

AC:

1463

AN:

152226

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0257

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00615

Gnomad ASJ

AF:

0.000865

Gnomad EAS

AF:

0.0112

Gnomad SAS

AF:

0.0151

Gnomad FIN

AF:

0.00104

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00215

Gnomad OTH

AF:

0.00621

GnomAD4 exome

AF:

0.00530

AC:

2920

AN:

551178

Hom.:

Cov.:

AF XY:

0.00561

AC XY:

1662

AN XY:

296346

show subpopulations

Gnomad4 AFR exome

AF:

0.0260

Gnomad4 AMR exome

AF:

0.00421

Gnomad4 ASJ exome

AF:

0.00171

Gnomad4 EAS exome

AF:

0.0188

Gnomad4 SAS exome

AF:

0.0132

Gnomad4 FIN exome

AF:

0.00123

Gnomad4 NFE exome

AF:

0.00203

Gnomad4 OTH exome

AF:

0.00575

GnomAD4 genome

AF:

0.00969

AC:

1476

AN:

152344

Hom.:

Cov.:

AF XY:

0.0102

AC XY:

763

AN XY:

74496

show subpopulations

Gnomad4 AFR

AF:

0.0259

Gnomad4 AMR

AF:

0.00614

Gnomad4 ASJ

AF:

0.000865

Gnomad4 EAS

AF:

0.0112

Gnomad4 SAS

AF:

0.0153

Gnomad4 FIN

AF:

0.00104

Gnomad4 NFE

AF:

0.00215

Gnomad4 OTH

AF:

0.00614

Alfa

AF:

0.00491

Hom.:

Bravo

AF:

0.0108

Asia WGS

AF:

0.0230

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Oct 27, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

3.5

DANN

Benign

0.63

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