rs363333

chr10-117244584-C-T

Variant summary

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

The NM_003054.6(SLC18A2):c.464+271C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.758 in 152,226 control chromosomes in the GnomAD database, including 47,929 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 0.76 (47929 hom., cov: 33)
• Consequence: SLC18A2 NM_003054.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.438

Genes affected

SLC18A2 (HGNC:10935): (solute carrier family 18 member A2) This gene encodes an transmembrane protein that functions as an ATP-dependent transporter of monoamines, such as dopamine, norepinephrine, serotonin, and histamine. This protein transports amine neurotransmitters into synaptic vesicles. Polymorphisms in this gene may be associated with schizophrenia, bipolar disorder, and other neurological/psychiatric ailments. [provided by RefSeq, Jun 2018]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.926 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC18A2	NM_003054.6	c.464+271C>T		intron_variant		ENST00000644641.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC18A2	ENST00000644641.2	c.464+271C>T		intron_variant			NM_003054.6	P1
SLC18A2	ENST00000497497.1	n.607+271C>T		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.758 AC: 115318 AN: 152108 Hom.: 47921 Cov.: 33

Gnomad AFR AF: 0.392

Gnomad AMI AF: 0.974

Gnomad AMR AF: 0.772

Gnomad ASJ AF: 0.915

Gnomad EAS AF: 0.720

Gnomad SAS AF: 0.902

Gnomad FIN AF: 0.927

Gnomad MID AF: 0.845

Gnomad NFE AF: 0.932

Gnomad OTH AF: 0.778

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

GnomAD4 genome AF: 0.758 AC: 115341 AN: 152226 Hom.: 47929 Cov.: 33 AF XY: 0.760 AC XY: 56587 AN XY: 74426

Gnomad4 AFR AF: 0.391

Gnomad4 AMR AF: 0.772

Gnomad4 ASJ AF: 0.915

Gnomad4 EAS AF: 0.720

Gnomad4 SAS AF: 0.902

Gnomad4 FIN AF: 0.927

Gnomad4 NFE AF: 0.932

Gnomad4 OTH AF: 0.778

Alfa AF: 0.893 Hom.: 81526

Bravo AF: 0.724

Asia WGS AF: 0.779 AC: 2711 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
Cadd	Benign	6.1
Dann	Benign	0.55

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: rs363333; hg19: chr10-119004095;