5-1409012-T-C

Variant names:

• chr5-1409012-T-C
• rs429699
• NM_001044.5:c.1498+14A>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001044.5(SLC6A3):​c.1498+14A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.985 in 1,590,154 control chromosomes in the GnomAD database, including 773,574 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.98 (73149 hom., cov: 33)
  • Exomes 𝑓: 0.99 (700425 hom.)
• Consequence: SLC6A3 NM_001044.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:7
• Conservation: PhyloP100: -0.513
• Publications: 21 publications found

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 Gene-Disease associations (from GenCC):

• classic dopamine transporter deficiency syndrome

  Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P
• SLC6A3-related dopamine transporter deficiency syndrome

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• parkinsonism-dystonia, infantile

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 5-1409012-T-C is Benign according to our data. Variant chr5-1409012-T-C is described in ClinVar as Benign. ClinVar VariationId is 518359.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.992 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC6A3	NM_001044.5	c.1498+14A>G		intron_variant	Intron 11 of 14	ENST00000270349.12	NP_001035.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC6A3	ENST00000270349.12	c.1498+14A>G		intron_variant	Intron 11 of 14	1	NM_001044.5	ENSP00000270349.9
SLC6A3	ENST00000713697.1	n.*383A>G		non_coding_transcript_exon_variant	Exon 11 of 11			ENSP00000519001.1
SLC6A3	ENST00000713697.1	n.*383A>G		3_prime_UTR_variant	Exon 11 of 11			ENSP00000519001.1
SLC6A3	ENST00000713696.1	c.1363+14A>G		intron_variant	Intron 10 of 14			ENSP00000519000.1

Frequencies

GnomAD3 genomes AF: 0.979 AC: 148918 AN: 152186 Hom.: 73085 Cov.: 33

Gnomad AFR AF: 0.994

Gnomad AMI AF: 0.913

Gnomad AMR AF: 0.904

Gnomad ASJ AF: 0.999

Gnomad EAS AF: 0.758

Gnomad SAS AF: 0.984

Gnomad FIN AF: 1.00

Gnomad MID AF: 1.00

Gnomad NFE AF: 0.999

Gnomad OTH AF: 0.970

GnomAD2 exomes AF: 0.958 AC: 237208 AN: 247528 AF XY: 0.965

Gnomad AFR exome AF: 0.995

Gnomad AMR exome AF: 0.854

Gnomad ASJ exome AF: 0.998

Gnomad EAS exome AF: 0.754

Gnomad FIN exome AF: 1.00

Gnomad NFE exome AF: 0.999

Gnomad OTH exome AF: 0.970

GnomAD4 exome AF: 0.986 AC: 1417270 AN: 1437850 Hom.: 700425 Cov.: 26 AF XY: 0.986 AC XY: 706891 AN XY: 716654

African (AFR) AF: 0.997 AC: 32908 AN: 33022

American (AMR) AF: 0.860 AC: 38325 AN: 44554

Ashkenazi Jewish (ASJ) AF: 0.998 AC: 25939 AN: 25980

East Asian (EAS) AF: 0.730 AC: 28856 AN: 39512

South Asian (SAS) AF: 0.985 AC: 84316 AN: 85580

European-Finnish (FIN) AF: 1.00 AC: 52112 AN: 52118

Middle Eastern (MID) AF: 0.991 AC: 5646 AN: 5696

European-Non Finnish (NFE) AF: 0.999 AC: 1091039 AN: 1091814

Other (OTH) AF: 0.976 AC: 58129 AN: 59574

GnomAD4 genome AF: 0.979 AC: 149041 AN: 152304 Hom.: 73149 Cov.: 33 AF XY: 0.976 AC XY: 72678 AN XY: 74458

African (AFR) AF: 0.994 AC: 41333 AN: 41576

American (AMR) AF: 0.904 AC: 13826 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.999 AC: 3469 AN: 3472

East Asian (EAS) AF: 0.758 AC: 3904 AN: 5150

South Asian (SAS) AF: 0.985 AC: 4756 AN: 4830

European-Finnish (FIN) AF: 1.00 AC: 10618 AN: 10618

Middle Eastern (MID) AF: 0.997 AC: 293 AN: 294

European-Non Finnish (NFE) AF: 0.999 AC: 67955 AN: 68038

Other (OTH) AF: 0.971 AC: 2054 AN: 2116

Alfa AF: 0.992 Hom.: 17882

Bravo AF: 0.969

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Classic dopamine transporter deficiency syndrome Benign:4

Sep 21, 2015

Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jul 14, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Feb 07, 2015

Genome Diagnostics Laboratory, Amsterdam University Medical Center

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jul 05, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Parkinsonism-dystonia, infantile Benign:1

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.33
DANN	Benign	0.26
PhyloP100		-0.51
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs429699; hg19: chr5-1409127; COSMIC: COSV54362635;