Genetic Variant SLC6A3:c.1031+71G>C (chr5-1416027-C-G) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001044.5(SLC6A3):c.1031+71G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,096 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 34)

Exomes 𝑓: 0.000013 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

SLC6A3
NM_001044.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -3.14

Publications

16 publications found

Variant links:

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

SLC6A3 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-1.0).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC6A3	NM_001044.5 link	c.1031+71G>C		intron_variant	Intron 7 of 14	ENST00000270349.12	NP_001035.1	Q01959

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
SLC6A3	ENST00000270349.12 link	c.1031+71G>C	intron_variant	Intron 7 of 14	1	NM_001044.5	ENSP00000270349.9	Q01959
SLC6A3	ENST00000713696.1 link	c.896+71G>C	intron_variant	Intron 6 of 14			ENSP00000519000.1
SLC6A3	ENST00000511750.1 link	n.481+71G>C	intron_variant	Intron 1 of 1	4
SLC6A3	ENST00000713697.1 link	n.1031+71G>C	intron_variant	Intron 7 of 10			ENSP00000519001.1

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152096

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000128

AC:

AN:

1016864

Hom.:

AF XY:

0.0000153

AC XY:

AN XY:

524198

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

25016

American (AMR)

AF:

0.00

AC:

AN:

42870

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

23236

East Asian (EAS)

AF:

0.000160

AC:

AN:

37390

South Asian (SAS)

AF:

0.00

AC:

AN:

76948

European-Finnish (FIN)

AF:

0.00

AC:

AN:

51444

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4916

European-Non Finnish (NFE)

AF:

0.00000987

AC:

AN:

709182

Other (OTH)

AF:

0.00

AC:

AN:

45862

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152096

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74290

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41396

American (AMR)

AF:

0.00

AC:

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5184

South Asian (SAS)

AF:

0.00

AC:

AN:

4822

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10606

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

68020

Other (OTH)

AF:

0.00

AC:

AN:

2086

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.625

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

83879

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-1.0

CADD

Benign

0.0080

(source)

DANN

Benign

0.17

PhyloP100

-3.1

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over