rs363223

Variant names:

• chr10-117263050-G-A
• rs363223
• NM_003054.6:c.992-3683G>A

Your query was ambiguous. Multiple possible variants found:

• chr10-117263050-G-A
• chr10-117263050-G-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.992-3683G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.468 in 152,046 control chromosomes in the GnomAD database, including 17,499 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 0.47 (17499 hom., cov: 32)
• Consequence: SLC18A2 NM_003054.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.657
• Publications: 3 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=-0.8).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.537 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC18A2	NM_003054.6	c.992-3683G>A		intron_variant	Intron 10 of 15	ENST00000644641.2	NP_003045.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC18A2	ENST00000644641.2	c.992-3683G>A		intron_variant	Intron 10 of 15		NM_003054.6	ENSP00000496339.1
SLC18A2	ENST00000497497.1	n.1408-3683G>A		intron_variant	Intron 9 of 14	2

Frequencies

GnomAD3 genomes AF: 0.468 AC: 71117 AN: 151928 Hom.: 17501 Cov.: 32

Gnomad AFR AF: 0.312

Gnomad AMI AF: 0.629

Gnomad AMR AF: 0.522

Gnomad ASJ AF: 0.458

Gnomad EAS AF: 0.453

Gnomad SAS AF: 0.496

Gnomad FIN AF: 0.515

Gnomad MID AF: 0.370

Gnomad NFE AF: 0.542

Gnomad OTH AF: 0.472

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

GnomAD4 genome AF: 0.468 AC: 71131 AN: 152046 Hom.: 17499 Cov.: 32 AF XY: 0.467 AC XY: 34671 AN XY: 74310

African (AFR) AF: 0.312 AC: 12938 AN: 41476

American (AMR) AF: 0.522 AC: 7973 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.458 AC: 1590 AN: 3470

East Asian (EAS) AF: 0.452 AC: 2333 AN: 5158

South Asian (SAS) AF: 0.496 AC: 2387 AN: 4814

European-Finnish (FIN) AF: 0.515 AC: 5441 AN: 10574

Middle Eastern (MID) AF: 0.361 AC: 106 AN: 294

European-Non Finnish (NFE) AF: 0.541 AC: 36806 AN: 67972

Other (OTH) AF: 0.469 AC: 985 AN: 2102

Alfa AF: 0.403 Hom.: 1722

Bravo AF: 0.466

Asia WGS AF: 0.454 AC: 1579 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	2.1
DANN	Benign	0.54
PhyloP100		0.66
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs363223; hg19: chr10-119022561;