rs3523

Variant names:

• chr10-117273945-T-A
• rs3523
• NM_003054.6:c.1441-3217T>A

Your query was ambiguous. Multiple possible variants found:

• chr10-117273945-T-A
• chr10-117273945-T-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.1441-3217T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.768 in 152,064 control chromosomes in the GnomAD database, including 45,537 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 0.77 (45537 hom., cov: 31)
• Consequence: SLC18A2 NM_003054.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.83
• Publications: 5 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=-0.85).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.843 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC18A2	NM_003054.6	c.1441-3217T>A		intron_variant	Intron 15 of 15	ENST00000644641.2	NP_003045.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC18A2	ENST00000644641.2	c.1441-3217T>A		intron_variant	Intron 15 of 15		NM_003054.6	ENSP00000496339.1
SLC18A2	ENST00000497497.1	n.1857-3217T>A		intron_variant	Intron 14 of 14	2

Frequencies

GnomAD3 genomes AF: 0.768 AC: 116740 AN: 151946 Hom.: 45511 Cov.: 31

Gnomad AFR AF: 0.649

Gnomad AMI AF: 0.914

Gnomad AMR AF: 0.742

Gnomad ASJ AF: 0.818

Gnomad EAS AF: 0.565

Gnomad SAS AF: 0.741

Gnomad FIN AF: 0.841

Gnomad MID AF: 0.747

Gnomad NFE AF: 0.848

Gnomad OTH AF: 0.763

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

GnomAD4 genome AF: 0.768 AC: 116818 AN: 152064 Hom.: 45537 Cov.: 31 AF XY: 0.764 AC XY: 56786 AN XY: 74322

African (AFR) AF: 0.650 AC: 26938 AN: 41450

American (AMR) AF: 0.741 AC: 11311 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.818 AC: 2838 AN: 3470

East Asian (EAS) AF: 0.564 AC: 2911 AN: 5160

South Asian (SAS) AF: 0.740 AC: 3566 AN: 4820

European-Finnish (FIN) AF: 0.841 AC: 8899 AN: 10584

Middle Eastern (MID) AF: 0.752 AC: 221 AN: 294

European-Non Finnish (NFE) AF: 0.848 AC: 57692 AN: 68000

Other (OTH) AF: 0.762 AC: 1608 AN: 2110

Alfa AF: 0.806 Hom.: 6238

Bravo AF: 0.757

Asia WGS AF: 0.634 AC: 2205 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	2.9
DANN	Benign	0.68
PhyloP100		-1.8
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: rs3523; hg19: chr10-119033456;