NM_001044.5:c.1858G>T

Variant names:

• chr5-1394740-C-A
• NM_001044.5:c.1858G>T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001044.5(SLC6A3):​c.1858G>T​(p.Val620Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,850 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: SLC6A3 NM_001044.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.80

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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.17887068).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC6A3	NM_001044.5	c.1858G>T	p.Val620Leu	missense_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.1858G>T	p.Val620Leu	missense_variant	Exon 15 of 15	1	NM_001044.5	ENSP00000270349.9
SLC6A3	ENST00000512002.2	n.239G>T		non_coding_transcript_exon_variant	Exon 3 of 3	1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461850 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 727222

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000116

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.068	T
BayesDel_noAF	Benign	-0.33
CADD	Benign	16
DANN	Uncertain	1.0
DEOGEN2	Benign	0.26	T
Eigen	Benign	-0.39
Eigen_PC	Benign	-0.24
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Benign	0.48	T
M_CAP	Benign	0.036	D
MetaRNN	Benign	0.18	T
MetaSVM	Benign	-0.88	T
MutationAssessor	Benign	1.7	L
PrimateAI	Uncertain	0.62	T
PROVEAN	Benign	-0.58	N
REVEL	Benign	0.082
Sift	Benign	0.16	T
Sift4G	Benign	0.079	T
Polyphen		0.019	B
Vest4		0.23
MutPred		0.34		Loss of methylation at K619 (P = 0.0298);
MVP		0.62
MPC		0.61
ClinPred		0.38	T
GERP RS		3.9
Varity_R		0.11
gMVP		0.19

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr5-1394855; COSMIC: COSV54362109;