5-1394407-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

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
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.06

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]

ACMG classification

Verdict is Benign. Variant got -14 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_single_submitter, 1 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/exons	MANE	UniProt
SLC6A3	NM_001044.5	c.*328G>A		3_prime_UTR_variant	15/15	ENST00000270349.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC6A3	ENST00000270349.12	c.*328G>A		3_prime_UTR_variant	15/15	1	NM_001044.5	P1
SLC6A3	ENST00000512002.2	n.572G>A		non_coding_transcript_exon_variant	3/3	1

Frequencies

GnomAD3 genomes AF: 0.176 AC: 26786 AN: 151990 Hom.: 2488 Cov.: 32

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.: 0 AF XY: 0.197 AC XY: 35422 AN XY: 179792

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.: 32 AF XY: 0.179 AC XY: 13329 AN XY: 74348

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:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 15, 2020

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

Other links and lift over

dbSNP: rs27072; hg19: chr5-1394522;