10-117244568-G-C

Position:

• chr10-117244568-G-C

Variant summary

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

The NM_003054.6(SLC18A2):​c.464+255G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.192 in 152,290 control chromosomes in the GnomAD database, including 3,756 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 0.19 (3756 hom., cov: 33)
• Consequence: SLC18A2 NM_003054.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.554

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]

SLC18A2 (HGNC:):

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 (EAS) allele frequency at 95% confidence interval = 0.555 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC18A2	NM_003054.6	c.464+255G>C		intron_variant		ENST00000644641.2	NP_003045.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC18A2	ENST00000644641.2	c.464+255G>C		intron_variant			NM_003054.6	ENSP00000496339.1
SLC18A2	ENST00000497497.1	n.607+255G>C		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.192 AC: 29200 AN: 152172 Hom.: 3747 Cov.: 33

Gnomad AFR AF: 0.0612

Gnomad AMI AF: 0.416

Gnomad AMR AF: 0.158

Gnomad ASJ AF: 0.171

Gnomad EAS AF: 0.572

Gnomad SAS AF: 0.334

Gnomad FIN AF: 0.170

Gnomad MID AF: 0.159

Gnomad NFE AF: 0.242

Gnomad OTH AF: 0.188

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

GnomAD4 genome AF: 0.192 AC: 29218 AN: 152290 Hom.: 3756 Cov.: 33 AF XY: 0.191 AC XY: 14230 AN XY: 74460

Gnomad4 AFR AF: 0.0610

Gnomad4 AMR AF: 0.158

Gnomad4 ASJ AF: 0.171

Gnomad4 EAS AF: 0.572

Gnomad4 SAS AF: 0.334

Gnomad4 FIN AF: 0.170

Gnomad4 NFE AF: 0.242

Gnomad4 OTH AF: 0.196

Alfa AF: 0.207 Hom.: 455

Bravo AF: 0.185

Asia WGS AF: 0.445 AC: 1547 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	4.0
DANN	Benign	0.36

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		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: rs363390; hg19: chr10-119004079;