Genetic Variant SLC6A3:c.*950_*989delTGGAGCGTGTACTACCCCAGGACGCATGCAGGGCCCCCAC (chr5-1393745-TGTGGGGGCCCTGCATGCGTCCTGGGGTAGTACACGCTCCA-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_001044.5(SLC6A3):c.*950_*989delTGGAGCGTGTACTACCCCAGGACGCATGCAGGGCCCCCAC variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. It is difficult to determine the true allele frequency of this variant because it is of type DEL_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000054 ( 0 hom., cov: 20)

Consequence

SLC6A3
NM_001044.5 3_prime_UTR

Scores

Not classified

Clinical Significance

Uncertain risk allele criteria provided, single submitter O:1

Conservation

PhyloP100: 1.63

Publications

116 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: Uncertain_significance. The variant received 0 ACMG points.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC6A3	NM_001044.5 link	c.950_989delTGGAGCGTGTACTACCCCAGGACGCATGCAGGGCCCCCAC		3_prime_UTR_variant	Exon 15 of 15	ENST00000270349.12	NP_001035.1	Q01959

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC6A3	ENST00000270349.12 link	c.950_989delTGGAGCGTGTACTACCCCAGGACGCATGCAGGGCCCCCAC		3_prime_UTR_variant	Exon 15 of 15	1	NM_001044.5	ENSP00000270349.9		Q01959
SLC6A3	ENST00000512002.2 link	n.244_283delTGGAGCGTGTACTACCCCAGGACGCATGCAGGGCCCCCAC		downstream_gene_variant		1

Frequencies

GnomAD3 genomes

AF:

0.0000537

AC:

AN:

130330

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000303

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000799

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000259

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000632

Gnomad OTH

AF:

0.00

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.0000537

AC:

AN:

130370

Hom.:

Cov.:

AF XY:

0.0000481

AC XY:

AN XY:

62376

show subpopulations

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.0000303

AC:

AN:

33052

American (AMR)

AF:

0.0000798

AC:

AN:

12532

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3292

East Asian (EAS)

AF:

0.00

AC:

AN:

4274

South Asian (SAS)

AF:

0.000260

AC:

AN:

3844

European-Finnish (FIN)

AF:

0.00

AC:

AN:

7286

Middle Eastern (MID)

AF:

0.00

AC:

AN:

210

European-Non Finnish (NFE)

AF:

0.0000633

AC:

AN:

63234

Other (OTH)

AF:

0.00

AC:

AN:

1816

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.361

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

ClinVar

Significance: Uncertain risk allele

Submissions summary: Other:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Schizophrenia

Other:1

Center for Forensic Mental Health, Chiba University

Significance:Uncertain risk allele

Review Status:criteria provided, single submitter

Collection Method:case-control

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Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

1.6

Splicing

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

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over