Genetic Variant NM_001044.5:c.*796_*835delGTGTCCTATCCCCGGACGCATGCAGGGCCCCCACAGGAGC (chr5-1393899-TGCTCCTGTGGGGGCCCTGCATGCGTCCGGGGATAGGACAC-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.*796_*835delGTGTCCTATCCCCGGACGCATGCAGGGCCCCCACAGGAGC variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00032 in 3,122 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.00023 ( 0 hom., cov: 30)

Exomes 𝑓: 0.00032 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

SLC6A3
NM_001044.5 3_prime_UTR

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.53

Publications

0 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.796_835delGTGTCCTATCCCCGGACGCATGCAGGGCCCCCACAGGAGC		3_prime_UTR_variant	Exon 15 of 15	ENST00000270349.12	NP_001035.1	Q01959

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
SLC6A3	ENST00000270349.12 link	c.796_835delGTGTCCTATCCCCGGACGCATGCAGGGCCCCCACAGGAGC	3_prime_UTR_variant	Exon 15 of 15	1	NM_001044.5	ENSP00000270349.9	Q01959
SLC6A3	ENST00000512002.2 link	n.90_129delGTGTCCTATCCCCGGACGCATGCAGGGCCCCCACAGGAGC	downstream_gene_variant		1
SLC6A3	ENST00000713696.1 link	c.854_893delGTGTCCTATCCCCGGACGCATGCAGGGCCCCCACAGGAGC	downstream_gene_variant				ENSP00000519000.1

Frequencies

GnomAD3 genomes

AF:

0.000233

AC:

AN:

94238

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000395

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000110

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000700

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000211

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.000320

AC:

AN:

3122

Hom.:

AF XY:

0.000590

AC XY:

AN XY:

1694

show subpopulations

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

African (AFR)

AF:

0.00

AC:

AN:

American (AMR)

AF:

0.00

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

East Asian (EAS)

AF:

0.00

AC:

AN:

South Asian (SAS)

AF:

0.00

AC:

AN:

102

European-Finnish (FIN)

AF:

0.00

AC:

AN:

468

Middle Eastern (MID)

AF:

0.00

AC:

AN:

1584

European-Non Finnish (NFE)

AF:

0.00157

AC:

AN:

638

Other (OTH)

AF:

0.00

AC:

AN:

224

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 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: 0.225

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000233

AC:

AN:

94274

Hom.:

Cov.:

AF XY:

0.000178

AC XY:

AN XY:

45048

show subpopulations

African (AFR)

AF:

0.000395

AC:

AN:

22798

American (AMR)

AF:

0.000110

AC:

AN:

9086

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2528

East Asian (EAS)

AF:

0.000701

AC:

AN:

2854

South Asian (SAS)

AF:

0.00

AC:

AN:

2650

European-Finnish (FIN)

AF:

0.00

AC:

AN:

4866

Middle Eastern (MID)

AF:

0.00

AC:

AN:

128

European-Non Finnish (NFE)

AF:

0.000211

AC:

AN:

47452

Other (OTH)

AF:

0.00

AC:

AN:

1346

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.420

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome 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

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

1.5

Splicing

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

Publications

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NM_001044.5:c.796_835delGTGTCCTATCCCCGGACGCATGCAGGGCCCCCACAGGAGC

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