rs2975223

Positions:

• chr5-1443488-T-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001044.5(SLC6A3):​c.-45-246A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.502 in 151,378 control chromosomes in the GnomAD database, including 20,008 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.50 (20008 hom., cov: 32)
• Consequence: SLC6A3 NM_001044.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.87

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 5-1443488-T-C is Benign according to our data. Variant chr5-1443488-T-C is described in ClinVar as [Benign]. Clinvar id is 1261279.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.589 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC6A3	NM_001044.5	c.-45-246A>G		intron_variant		ENST00000270349.12	NP_001035.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC6A3	ENST00000270349.12	c.-45-246A>G		intron_variant		1	NM_001044.5	ENSP00000270349	P1

Frequencies

GnomAD3 genomes AF: 0.502 AC: 75864 AN: 151260 Hom.: 19981 Cov.: 32

Gnomad AFR AF: 0.372

Gnomad AMI AF: 0.630

Gnomad AMR AF: 0.480

Gnomad ASJ AF: 0.614

Gnomad EAS AF: 0.169

Gnomad SAS AF: 0.510

Gnomad FIN AF: 0.554

Gnomad MID AF: 0.567

Gnomad NFE AF: 0.593

Gnomad OTH AF: 0.519

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

GnomAD4 genome AF: 0.502 AC: 75946 AN: 151378 Hom.: 20008 Cov.: 32 AF XY: 0.500 AC XY: 36939 AN XY: 73920

Gnomad4 AFR AF: 0.372

Gnomad4 AMR AF: 0.480

Gnomad4 ASJ AF: 0.614

Gnomad4 EAS AF: 0.169

Gnomad4 SAS AF: 0.512

Gnomad4 FIN AF: 0.554

Gnomad4 NFE AF: 0.594

Gnomad4 OTH AF: 0.522

Alfa AF: 0.538 Hom.: 2740

Bravo AF: 0.487

Asia WGS AF: 0.372 AC: 1293 AN: 3476

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Mar 31, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.045
DANN	Benign	0.49

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs2975223; hg19: chr5-1443603; COSMIC: COSV54362263;