10-117250954-C-T

Variant names:

• chr10-117250954-C-T
• rs363341
• NM_003054.6:c.465-2445C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003054.6(SLC18A2):​c.465-2445C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.309 in 152,020 control chromosomes in the GnomAD database, including 8,042 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 0.31 (8042 hom., cov: 32)
• Consequence: SLC18A2 NM_003054.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.261
• Publications: 6 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=-0.95).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.635 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC18A2	NM_003054.6	c.465-2445C>T		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.465-2445C>T		intron_variant	Intron 3 of 15		NM_003054.6	ENSP00000496339.1
SLC18A2	ENST00000497497.1	n.608-2445C>T		intron_variant	Intron 3 of 14	2

Frequencies

GnomAD3 genomes AF: 0.309 AC: 46873 AN: 151902 Hom.: 8018 Cov.: 32

Gnomad AFR AF: 0.401

Gnomad AMI AF: 0.418

Gnomad AMR AF: 0.214

Gnomad ASJ AF: 0.183

Gnomad EAS AF: 0.654

Gnomad SAS AF: 0.399

Gnomad FIN AF: 0.183

Gnomad MID AF: 0.171

Gnomad NFE AF: 0.267

Gnomad OTH AF: 0.269

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

GnomAD4 genome AF: 0.309 AC: 46954 AN: 152020 Hom.: 8042 Cov.: 32 AF XY: 0.305 AC XY: 22668 AN XY: 74334

African (AFR) AF: 0.401 AC: 16607 AN: 41416

American (AMR) AF: 0.215 AC: 3285 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.183 AC: 636 AN: 3466

East Asian (EAS) AF: 0.653 AC: 3373 AN: 5166

South Asian (SAS) AF: 0.399 AC: 1920 AN: 4814

European-Finnish (FIN) AF: 0.183 AC: 1942 AN: 10596

Middle Eastern (MID) AF: 0.163 AC: 48 AN: 294

European-Non Finnish (NFE) AF: 0.267 AC: 18179 AN: 67974

Other (OTH) AF: 0.277 AC: 583 AN: 2108

Alfa AF: 0.282 Hom.: 17110

Bravo AF: 0.316

Asia WGS AF: 0.535 AC: 1858 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	1.2
DANN	Benign	0.20
PhyloP100		-0.26
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: rs363341; hg19: chr10-119010465;