NM_001044.5:c.*835_*836insGTGTCCTATCCCCGGACGCATGCAGGGCCCCCACAGGAGCGTGTCCTATCCCCGGACGCATGCAGGGCCCCCACAGGAGCGTGTCCTATCCCCGGACGCATGCAGGGCCCCCACAGGAGCGTGTCCTATCCCCGGACGCATGCAGGGCCCCCACAGGAGCGTGTCCTATCCCCGGACGCATGCAGGGCCCCCACAGGAGCGTGTCCTATCCCCGGACGCATGCAGGGCCCCCACAGGAGCGTGTCCTATCCCCGGACGCATGCAGGGCCCCCACAGGAGC

Variant names:

• chr5-1393899-T-TGCTCCTGTGGGGGCCCTGCATGCGTCCGGGGATAGGACACGCTCCTGTGGGGGCCCTGCATGCGTCCGGGGATAGGACACGCTCCTGTGGGGGCCCTGCATGCGTCCGGGGATAGGACACGCTCCTGTGGGGGCCCTGCATGCGTCCGGGGATAGGACACGCTCCTGTGGGGGCCCTGCATGCGTCCGGGGATAGGACACGCTCCTGTGGGGGCCCTGCATGCGTCCGGGGATAGGACACGCTCCTGTGGGGGCCCTGCATGCGTCCGGGGATAGGACAC
• rs1755646498
• NM_001044.5:c.*835_*836insGTGTCCTATCCCCGGACGCATGCAGGGCCCCCACAGGAGCGTGTCCTATCCCCGGACGCATGCAGGGCCCCCACAGGAGCGTGTCCTATCCCCGGACGCATGCAGGGCCCCCACAGGAGCGTGTCCTATCCCCGGACGCATGCAGGGCCCCCACAGGAGCGTGTCCTATCCCCGGACGCATGCAGGGCCCCCACAGGAGCGTGTCCTATCCCCGGACGCATGCAGGGCCCCCACAGGAGCGTGTCCTATCCCCGGACGCATGCAGGGCCCCCACAGGAGC

Variant summary

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

The NM_001044.5(SLC6A3):​c.*835_*836insGTGTCCTATCCCCGGACGCATGCAGGGCCCCCACAGGAGCGTGTCCTATCCCCGGACGCATGCAGGGCCCCCACAGGAGCGTGTCCTATCCCCGGACGCATGCAGGGCCCCCACAGGAGCGTGTCCTATCCCCGGACGCATGCAGGGCCCCCACAGGAGCGTGTCCTATCCCCGGACGCATGCAGGGCCCCCACAGGAGCGTGTCCTATCCCCGGACGCATGCAGGGCCCCCACAGGAGCGTGTCCTATCCCCGGACGCATGCAGGGCCCCCACAGGAGC variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type INS_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: not found (cov: 30)
• Consequence: SLC6A3 NM_001044.5 3_prime_UTR
• Clinical Significance: protective no assertion criteria provided B:1
• Conservation: PhyloP100: 0.355
• Publications: 0 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: Uncertain_significance. The variant received 0 ACMG points.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC6A3	NM_001044.5	c.*835_*836insGTGTCCTATCCCCGGACGCATGCAGGGCCCCCACAGGAGCGTGTCCTATCCCCGGACGCATGCAGGGCCCCCACAGGAGCGTGTCCTATCCCCGGACGCATGCAGGGCCCCCACAGGAGCGTGTCCTATCCCCGGACGCATGCAGGGCCCCCACAGGAGCGTGTCCTATCCCCGGACGCATGCAGGGCCCCCACAGGAGCGTGTCCTATCCCCGGACGCATGCAGGGCCCCCACAGGAGCGTGTCCTATCCCCGGACGCATGCAGGGCCCCCACAGGAGC		3_prime_UTR_variant	Exon 15 of 15	ENST00000270349.12	NP_001035.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC6A3	ENST00000270349.12	c.*835_*836insGTGTCCTATCCCCGGACGCATGCAGGGCCCCCACAGGAGCGTGTCCTATCCCCGGACGCATGCAGGGCCCCCACAGGAGCGTGTCCTATCCCCGGACGCATGCAGGGCCCCCACAGGAGCGTGTCCTATCCCCGGACGCATGCAGGGCCCCCACAGGAGCGTGTCCTATCCCCGGACGCATGCAGGGCCCCCACAGGAGCGTGTCCTATCCCCGGACGCATGCAGGGCCCCCACAGGAGCGTGTCCTATCCCCGGACGCATGCAGGGCCCCCACAGGAGC		3_prime_UTR_variant	Exon 15 of 15	1	NM_001044.5	ENSP00000270349.9
SLC6A3	ENST00000512002.2	n.*129_*130insGTGTCCTATCCCCGGACGCATGCAGGGCCCCCACAGGAGCGTGTCCTATCCCCGGACGCATGCAGGGCCCCCACAGGAGCGTGTCCTATCCCCGGACGCATGCAGGGCCCCCACAGGAGCGTGTCCTATCCCCGGACGCATGCAGGGCCCCCACAGGAGCGTGTCCTATCCCCGGACGCATGCAGGGCCCCCACAGGAGCGTGTCCTATCCCCGGACGCATGCAGGGCCCCCACAGGAGCGTGTCCTATCCCCGGACGCATGCAGGGCCCCCACAGGAGC		downstream_gene_variant		1
SLC6A3	ENST00000713696.1	c.*893_*894insGTGTCCTATCCCCGGACGCATGCAGGGCCCCCACAGGAGCGTGTCCTATCCCCGGACGCATGCAGGGCCCCCACAGGAGCGTGTCCTATCCCCGGACGCATGCAGGGCCCCCACAGGAGCGTGTCCTATCCCCGGACGCATGCAGGGCCCCCACAGGAGCGTGTCCTATCCCCGGACGCATGCAGGGCCCCCACAGGAGCGTGTCCTATCCCCGGACGCATGCAGGGCCCCCACAGGAGCGTGTCCTATCCCCGGACGCATGCAGGGCCCCCACAGGAGC		downstream_gene_variant				ENSP00000519000.1

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome Cov.: 0

GnomAD4 genome Cov.: 30

ClinVar

Significance: protective

Submissions summary: Benign:1

Revision: no assertion criteria provided

Submissions by phenotype

Nicotine dependence, protection against Benign:1

Jan 01, 1999

OMIM

Significance: protective

Review Status: no assertion criteria provided

Collection Method: literature only

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.35

Splicing

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

Other links and lift over

dbSNP: rs1755646498; hg19: chr5-1394014;