Variant 5-1394407-C-T 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.*328G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.187 in 494,750 control chromosomes in the GnomAD database, including 9,367 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.18 ( 2492 hom., cov: 32)

Exomes 𝑓: 0.19 ( 6875 hom. )

Consequence

SLC6A3
NM_001044.5 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -2.06

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=-0.91).

BP6

Variant 5-1394407-C-T is Benign according to our data. Variant chr5-1394407-C-T is described in ClinVar as [Benign]. Clinvar id is 1288474.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.248 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC6A3	NM_001044.5 link	c.*328G>A		3_prime_UTR_variant	Exon 15 of 15	ENST00000270349.12	NP_001035.1	Q01959

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC6A3	ENST00000270349 link	c.*328G>A		3_prime_UTR_variant	Exon 15 of 15	1	NM_001044.5	ENSP00000270349.9		Q01959
SLC6A3	ENST00000512002.2 link	n.572G>A		non_coding_transcript_exon_variant	Exon 3 of 3	1

Frequencies

GnomAD3 genomes

AF:

0.176

AC:

26786

AN:

151990

Hom.:

2488

Cov.:

show subpopulations

Gnomad AFR

AF:

0.139

Gnomad AMI

AF:

0.171

Gnomad AMR

AF:

0.216

Gnomad ASJ

AF:

0.158

Gnomad EAS

AF:

0.252

Gnomad SAS

AF:

0.260

Gnomad FIN

AF:

0.193

Gnomad MID

AF:

0.182

Gnomad NFE

AF:

0.177

Gnomad OTH

AF:

0.162

GnomAD4 exome

AF:

0.192

AC:

65849

AN:

342642

Hom.:

6875

Cov.:

AF XY:

0.197

AC XY:

35422

AN XY:

179792

show subpopulations

Gnomad4 AFR exome

AF:

0.136

Gnomad4 AMR exome

AF:

0.226

Gnomad4 ASJ exome

AF:

0.176

Gnomad4 EAS exome

AF:

0.221

Gnomad4 SAS exome

AF:

0.259

Gnomad4 FIN exome

AF:

0.193

Gnomad4 NFE exome

AF:

0.178

Gnomad4 OTH exome

AF:

0.187

GnomAD4 genome

AF:

0.176

AC:

26810

AN:

152108

Hom.:

2492

Cov.:

AF XY:

0.179

AC XY:

13329

AN XY:

74348

show subpopulations

Gnomad4 AFR

AF:

0.139

Gnomad4 AMR

AF:

0.216

Gnomad4 ASJ

AF:

0.158

Gnomad4 EAS

AF:

0.252

Gnomad4 SAS

AF:

0.260

Gnomad4 FIN

AF:

0.193

Gnomad4 NFE

AF:

0.177

Gnomad4 OTH

AF:

0.168

Alfa

AF:

0.171

Hom.:

3377

Bravo

AF:

0.173

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jul 15, 2020

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is associated with the following publications: (PMID: 21525861) -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

1.6

DANN

Benign

0.42

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