chr10-117244568-G-C

Variant names:

• chr10-117244568-G-C
• rs363390
• NM_003054.6:c.464+255G>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 2 publications found

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 Gene-Disease associations (from GenCC):

• brain dopamine-serotonin vesicular transport disease

  Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: Orphanet, G2P
• parkinsonism-dystonia, infantile, 2

  Inheritance: AR Classification: STRONG, MODERATE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)
• schizophrenia

  Inheritance: Unknown Classification: NO_KNOWN Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
SLC18A2	NM_003054.6	c.464+255G>C		intron_variant	Intron 3 of 15	ENST00000644641.2	NP_003045.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC18A2	ENST00000644641.2	c.464+255G>C		intron_variant	Intron 3 of 15		NM_003054.6	ENSP00000496339.1
SLC18A2	ENST00000497497.1	n.607+255G>C		intron_variant	Intron 3 of 14	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

African (AFR) AF: 0.0610 AC: 2537 AN: 41578

American (AMR) AF: 0.158 AC: 2422 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.171 AC: 592 AN: 3472

East Asian (EAS) AF: 0.572 AC: 2958 AN: 5168

South Asian (SAS) AF: 0.334 AC: 1611 AN: 4828

European-Finnish (FIN) AF: 0.170 AC: 1803 AN: 10608

Middle Eastern (MID) AF: 0.147 AC: 43 AN: 292

European-Non Finnish (NFE) AF: 0.242 AC: 16459 AN: 68018

Other (OTH) AF: 0.196 AC: 414 AN: 2114

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
PhyloP100		0.55
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs363390; hg19: chr10-119004079;