5-1432710-G-C

Variant names:

• chr5-1432710-G-C
• rs460000
• NM_001044.5:c.419-12C>G

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 2P and 10B. PM2 BP4_Strong BP6_Moderate BS1

The NM_001044.5(SLC6A3):​c.419-12C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000344 in 1,454,370 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000034 (0 hom.)
• Consequence: SLC6A3 NM_001044.5 intron
• Scores: Splicing: ADA: 0.00005160
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.662
• Publications: 43 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: Benign. The variant received -8 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 5-1432710-G-C is Benign according to our data. Variant chr5-1432710-G-C is described in CliVar as Likely_benign. Clinvar id is 1937162.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr5-1432710-G-C is described in CliVar as Likely_benign. Clinvar id is 1937162.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr5-1432710-G-C is described in CliVar as Likely_benign. Clinvar id is 1937162.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr5-1432710-G-C is described in CliVar as Likely_benign. Clinvar id is 1937162.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr5-1432710-G-C is described in CliVar as Likely_benign. Clinvar id is 1937162.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr5-1432710-G-C is described in CliVar as Likely_benign. Clinvar id is 1937162.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population amr. GnomAdExome4 allele frequency = 0.00000344 (5/1454370) while in subpopulation AMR AF = 0.000113 (5/44396). AF 95% confidence interval is 0.0000438. There are 0 homozygotes in GnomAdExome4. There are 2 alleles in the male GnomAdExome4 subpopulation. Median coverage is 31. This position passed quality control check.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC6A3	NM_001044.5	c.419-12C>G		intron_variant	Intron 3 of 14	ENST00000270349.12	NP_001035.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC6A3	ENST00000270349.12	c.419-12C>G		intron_variant	Intron 3 of 14	1	NM_001044.5	ENSP00000270349.9
SLC6A3	ENST00000713696.1	c.419-12C>G		intron_variant	Intron 3 of 14			ENSP00000519000.1
SLC6A3	ENST00000713698.1	c.419-12C>G		intron_variant	Intron 3 of 4			ENSP00000519002.1
SLC6A3	ENST00000713697.1	n.419-12C>G		intron_variant	Intron 3 of 10			ENSP00000519001.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.0000162 AC: 4 AN: 246960 AF XY: 0.0000150

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000117

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000344 AC: 5 AN: 1454370 Hom.: 0 Cov.: 31 AF XY: 0.00000276 AC XY: 2 AN XY: 723902

African (AFR) AF: 0.00 AC: 0 AN: 33328

American (AMR) AF: 0.000113 AC: 5 AN: 44396

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26092

East Asian (EAS) AF: 0.00 AC: 0 AN: 39598

South Asian (SAS) AF: 0.00 AC: 0 AN: 86084

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53244

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5750

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1105700

Other (OTH) AF: 0.00 AC: 0 AN: 60178

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 20943

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Parkinsonism-dystonia, infantile Benign:1

Aug 07, 2023

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	2.7
DANN	Benign	0.30
PhyloP100		0.66

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000052
dbscSNV1_RF	Benign	0.022
SpliceAI score (max)		0.060		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs460000; hg19: chr5-1432825;