5-1396698-T-C

Position:

• chr5-1396698-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000270349.12(SLC6A3):​c.1840-1940A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.107 in 152,100 control chromosomes in the GnomAD database, including 1,159 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.11 (1159 hom., cov: 32)
• Consequence: SLC6A3 ENST00000270349.12 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.74

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.194 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC6A3	NM_001044.5	c.1840-1940A>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.1840-1940A>G		intron_variant		1	NM_001044.5	ENSP00000270349	P1
SLC6A3	ENST00000512002.2	n.221-1940A>G		intron_variant, non_coding_transcript_variant		1

Frequencies

GnomAD3 genomes AF: 0.107 AC: 16235 AN: 151982 Hom.: 1156 Cov.: 32

Gnomad AFR AF: 0.197

Gnomad AMI AF: 0.137

Gnomad AMR AF: 0.0515

Gnomad ASJ AF: 0.0499

Gnomad EAS AF: 0.0224

Gnomad SAS AF: 0.0756

Gnomad FIN AF: 0.0849

Gnomad MID AF: 0.0696

Gnomad NFE AF: 0.0796

Gnomad OTH AF: 0.0813

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

GnomAD4 genome AF: 0.107 AC: 16268 AN: 152100 Hom.: 1159 Cov.: 32 AF XY: 0.104 AC XY: 7721 AN XY: 74340

Gnomad4 AFR AF: 0.198

Gnomad4 AMR AF: 0.0513

Gnomad4 ASJ AF: 0.0499

Gnomad4 EAS AF: 0.0225

Gnomad4 SAS AF: 0.0765

Gnomad4 FIN AF: 0.0849

Gnomad4 NFE AF: 0.0796

Gnomad4 OTH AF: 0.0805

Alfa AF: 0.102 Hom.: 126

Bravo AF: 0.107

Asia WGS AF: 0.0580 AC: 200 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.23
DANN	Benign	0.18

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: rs11564773; hg19: chr5-1396813;