NM_003054.6:c.465-3521C>T

Variant names:

• chr10-117249878-C-T
• rs363338
• NM_003054.6:c.465-3521C>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.465-3521C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.574 in 152,002 control chromosomes in the GnomAD database, including 27,341 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 0.57 (27341 hom., cov: 32)
• Consequence: SLC18A2 NM_003054.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.12
• Publications: 10 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=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.685 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC18A2	NM_003054.6	c.465-3521C>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.465-3521C>T		intron_variant	Intron 3 of 15		NM_003054.6	ENSP00000496339.1
SLC18A2	ENST00000497497.1	n.608-3521C>T		intron_variant	Intron 3 of 14	2

Frequencies

GnomAD3 genomes AF: 0.575 AC: 87284 AN: 151884 Hom.: 27343 Cov.: 32

Gnomad AFR AF: 0.347

Gnomad AMI AF: 0.561

Gnomad AMR AF: 0.613

Gnomad ASJ AF: 0.756

Gnomad EAS AF: 0.202

Gnomad SAS AF: 0.565

Gnomad FIN AF: 0.784

Gnomad MID AF: 0.703

Gnomad NFE AF: 0.690

Gnomad OTH AF: 0.607

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

GnomAD4 genome AF: 0.574 AC: 87285 AN: 152002 Hom.: 27341 Cov.: 32 AF XY: 0.579 AC XY: 43005 AN XY: 74284

African (AFR) AF: 0.347 AC: 14364 AN: 41414

American (AMR) AF: 0.613 AC: 9362 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.756 AC: 2625 AN: 3470

East Asian (EAS) AF: 0.202 AC: 1046 AN: 5170

South Asian (SAS) AF: 0.565 AC: 2720 AN: 4816

European-Finnish (FIN) AF: 0.784 AC: 8275 AN: 10554

Middle Eastern (MID) AF: 0.704 AC: 207 AN: 294

European-Non Finnish (NFE) AF: 0.690 AC: 46914 AN: 67986

Other (OTH) AF: 0.599 AC: 1263 AN: 2110

Alfa AF: 0.645 Hom.: 38584

Bravo AF: 0.546

Asia WGS AF: 0.359 AC: 1252 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.061
DANN	Benign	0.56
PhyloP100		-2.1
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: rs363338; hg19: chr10-119009389;