10-117249360-T-C

Variant names:

• chr10-117249360-T-C
• rs363399
• NM_003054.6:c.465-4039T>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.465-4039T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.193 in 152,290 control chromosomes in the GnomAD database, including 3,768 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 (3768 hom., cov: 34)
• Consequence: SLC18A2 NM_003054.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.11
• Publications: 4 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=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.543 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC18A2	NM_003054.6	c.465-4039T>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.465-4039T>C		intron_variant	Intron 3 of 15		NM_003054.6	ENSP00000496339.1
SLC18A2	ENST00000497497.1	n.608-4039T>C		intron_variant	Intron 3 of 14	2

Frequencies

GnomAD3 genomes AF: 0.193 AC: 29402 AN: 152172 Hom.: 3757 Cov.: 34

Gnomad AFR AF: 0.0621

Gnomad AMI AF: 0.416

Gnomad AMR AF: 0.160

Gnomad ASJ AF: 0.171

Gnomad EAS AF: 0.560

Gnomad SAS AF: 0.341

Gnomad FIN AF: 0.170

Gnomad MID AF: 0.142

Gnomad NFE AF: 0.244

Gnomad OTH AF: 0.186

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

GnomAD4 genome AF: 0.193 AC: 29422 AN: 152290 Hom.: 3768 Cov.: 34 AF XY: 0.192 AC XY: 14320 AN XY: 74454

African (AFR) AF: 0.0619 AC: 2572 AN: 41572

American (AMR) AF: 0.160 AC: 2455 AN: 15312

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

East Asian (EAS) AF: 0.560 AC: 2895 AN: 5174

South Asian (SAS) AF: 0.341 AC: 1645 AN: 4828

European-Finnish (FIN) AF: 0.170 AC: 1806 AN: 10594

Middle Eastern (MID) AF: 0.136 AC: 40 AN: 294

European-Non Finnish (NFE) AF: 0.244 AC: 16626 AN: 68016

Other (OTH) AF: 0.195 AC: 412 AN: 2116

Alfa AF: 0.193 Hom.: 596

Bravo AF: 0.186

Asia WGS AF: 0.442 AC: 1534 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.32
DANN	Benign	0.35
PhyloP100		-1.1
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: rs363399; hg19: chr10-119008871;