Genetic Variant NM_001044.5: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

- -

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

NM_001044.5:c.950_989delTGGAGCGTGTACTACCCCAGGACGCATGCAGGGCCCCCAC

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