NM_003054.6:c.464+1943A>T

Variant names:

• chr10-117246256-A-T
• rs363393
• NM_003054.6:c.464+1943A>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.464+1943A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.143 in 152,284 control chromosomes in the GnomAD database, including 2,100 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 0.14 (2100 hom., cov: 33)
• Consequence: SLC18A2 NM_003054.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.442
• Publications: 2 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=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.19 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC18A2	NM_003054.6	c.464+1943A>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.464+1943A>T		intron_variant	Intron 3 of 15		NM_003054.6	ENSP00000496339.1
SLC18A2	ENST00000497497.1	n.607+1943A>T		intron_variant	Intron 3 of 14	2

Frequencies

GnomAD3 genomes AF: 0.143 AC: 21747 AN: 152164 Hom.: 2100 Cov.: 33

Gnomad AFR AF: 0.0382

Gnomad AMI AF: 0.186

Gnomad AMR AF: 0.134

Gnomad ASJ AF: 0.193

Gnomad EAS AF: 0.0131

Gnomad SAS AF: 0.0836

Gnomad FIN AF: 0.310

Gnomad MID AF: 0.213

Gnomad NFE AF: 0.193

Gnomad OTH AF: 0.158

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

GnomAD4 genome AF: 0.143 AC: 21743 AN: 152284 Hom.: 2100 Cov.: 33 AF XY: 0.147 AC XY: 10909 AN XY: 74454

African (AFR) AF: 0.0381 AC: 1586 AN: 41586

American (AMR) AF: 0.134 AC: 2044 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.193 AC: 671 AN: 3470

East Asian (EAS) AF: 0.0131 AC: 68 AN: 5190

South Asian (SAS) AF: 0.0839 AC: 405 AN: 4828

European-Finnish (FIN) AF: 0.310 AC: 3282 AN: 10586

Middle Eastern (MID) AF: 0.218 AC: 64 AN: 294

European-Non Finnish (NFE) AF: 0.193 AC: 13124 AN: 68010

Other (OTH) AF: 0.156 AC: 330 AN: 2112

Alfa AF: 0.171 Hom.: 355

Bravo AF: 0.124

Asia WGS AF: 0.0570 AC: 199 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.49
DANN	Benign	0.45
PhyloP100		-0.44
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: rs363393; hg19: chr10-119005767;