5-1394485-C-G

Position:

• chr5-1394485-C-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001044.5(SLC6A3):​c.*250G>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 0.223 in 610,794 control chromosomes in the GnomAD database, including 16,174 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.24 (4474 hom., cov: 33)
  • Exomes 𝑓: 0.22 (11700 hom.)
• Consequence: SLC6A3 NM_001044.5 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.552

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BP6: Variant 5-1394485-C-G is Benign according to our data. Variant chr5-1394485-C-G is described in ClinVar as [Benign]. Clinvar id is 1259994.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.287 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC6A3	NM_001044.5	c.*250G>C		3_prime_UTR_variant	15/15	ENST00000270349.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC6A3	ENST00000270349.12	c.*250G>C		3_prime_UTR_variant	15/15	1	NM_001044.5	P1
SLC6A3	ENST00000512002.2	n.494G>C		non_coding_transcript_exon_variant	3/3	1

Frequencies

GnomAD3 genomes AF: 0.240 AC: 36412 AN: 152012 Hom.: 4464 Cov.: 33

Gnomad AFR AF: 0.291

Gnomad AMI AF: 0.204

Gnomad AMR AF: 0.208

Gnomad ASJ AF: 0.272

Gnomad EAS AF: 0.0921

Gnomad SAS AF: 0.223

Gnomad FIN AF: 0.173

Gnomad MID AF: 0.358

Gnomad NFE AF: 0.236

Gnomad OTH AF: 0.260

GnomAD4 exome AF: 0.218 AC: 99808 AN: 458664 Hom.: 11700 Cov.: 3 AF XY: 0.217 AC XY: 52545 AN XY: 242270

Gnomad4 AFR exome AF: 0.297

Gnomad4 AMR exome AF: 0.157

Gnomad4 ASJ exome AF: 0.270

Gnomad4 EAS exome AF: 0.0802

Gnomad4 SAS exome AF: 0.214

Gnomad4 FIN exome AF: 0.181

Gnomad4 NFE exome AF: 0.234

Gnomad4 OTH exome AF: 0.239

GnomAD4 genome AF: 0.240 AC: 36455 AN: 152130 Hom.: 4474 Cov.: 33 AF XY: 0.237 AC XY: 17594 AN XY: 74378

Gnomad4 AFR AF: 0.292

Gnomad4 AMR AF: 0.208

Gnomad4 ASJ AF: 0.272

Gnomad4 EAS AF: 0.0918

Gnomad4 SAS AF: 0.223

Gnomad4 FIN AF: 0.173

Gnomad4 NFE AF: 0.236

Gnomad4 OTH AF: 0.256

Alfa AF: 0.230 Hom.: 555

Bravo AF: 0.246

Asia WGS AF: 0.161 AC: 561 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

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	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	2.3
DANN	Benign	0.35

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: rs11564774; hg19: chr5-1394600;