rs6348

Positions:

• chr5-1420686-G-A

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BA1

The NM_001044.5(SLC6A3):​c.810C>T​(p.Ala270=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.014 in 1,613,388 control chromosomes in the GnomAD database, including 2,576 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. A270A) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.073 (1319 hom., cov: 33)
  • Exomes 𝑓: 0.0079 (1257 hom.)
• Consequence: SLC6A3 NM_001044.5 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 2.44

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 -19 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.4).
• BP6: Variant 5-1420686-G-A is Benign according to our data. Variant chr5-1420686-G-A is described in ClinVar as [Benign]. Clinvar id is 470642.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-1420686-G-A is described in Lovd as [Likely_benign].
• BP7: Synonymous conserved (PhyloP=2.43 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.247 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC6A3	NM_001044.5	c.810C>T	p.Ala270=	synonymous_variant	6/15	ENST00000270349.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC6A3	ENST00000270349.12	c.810C>T	p.Ala270=	synonymous_variant	6/15	1	NM_001044.5	P1

Frequencies

GnomAD3 genomes AF: 0.0725 AC: 11038 AN: 152180 Hom.: 1321 Cov.: 33

Gnomad AFR AF: 0.252

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0265

Gnomad ASJ AF: 0.000576

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00518

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0348

Gnomad NFE AF: 0.000999

Gnomad OTH AF: 0.0463

GnomAD3 exomes AF: 0.0199 AC: 4979 AN: 250576 Hom.: 568 AF XY: 0.0146 AC XY: 1986 AN XY: 135618

Gnomad AFR exome AF: 0.259

Gnomad AMR exome AF: 0.0130

Gnomad ASJ exome AF: 0.00110

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00549

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000814

Gnomad OTH exome AF: 0.00948

GnomAD4 exome AF: 0.00791 AC: 11560 AN: 1461090 Hom.: 1257 Cov.: 33 AF XY: 0.00697 AC XY: 5066 AN XY: 726794

Gnomad4 AFR exome AF: 0.261

Gnomad4 AMR exome AF: 0.0146

Gnomad4 ASJ exome AF: 0.000459

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00544

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000536

Gnomad4 OTH exome AF: 0.0169

GnomAD4 genome AF: 0.0725 AC: 11049 AN: 152298 Hom.: 1319 Cov.: 33 AF XY: 0.0698 AC XY: 5200 AN XY: 74480

Gnomad4 AFR AF: 0.251

Gnomad4 AMR AF: 0.0265

Gnomad4 ASJ AF: 0.000576

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00518

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00100

Gnomad4 OTH AF: 0.0458

Alfa AF: 0.0224 Hom.: 490

Bravo AF: 0.0830

Asia WGS AF: 0.0120 AC: 42 AN: 3478

EpiCase AF: 0.00120

EpiControl AF: 0.00113

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Parkinsonism-dystonia, infantile Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 30, 2024

- -

not provided Benign:1

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	-0.40
CADD	Benign	11
DANN	Benign	0.75

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: rs6348; hg19: chr5-1420801;