5-1394545-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

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
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0280

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=-0.84).
• 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_single_submitter, 1 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 GnomAd at 25 AR gene

Transcripts

RefSeq

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

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC6A3	ENST00000270349.12	c.*190C>T		3_prime_UTR_variant	15/15	1	NM_001044.5	P1
SLC6A3	ENST00000512002.2	n.434C>T		non_coding_transcript_exon_variant	3/3	1

Frequencies

GnomAD3 genomes AF: 0.00961 AC: 1463 AN: 152226 Hom.: 25 Cov.: 33

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.: 31 Cov.: 5 AF XY: 0.00561 AC XY: 1662 AN XY: 296346

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.: 25 Cov.: 33 AF XY: 0.0102 AC XY: 763 AN XY: 74496

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.: 5

Bravo AF: 0.0108

Asia WGS AF: 0.0230 AC: 81 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

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

Other links and lift over

dbSNP: rs403798; hg19: chr5-1394660;