rs929493

Variant names:

• chr10-117259615-C-T
• rs929493
• NM_003054.6:c.991+1723C>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.991+1723C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.704 in 152,134 control chromosomes in the GnomAD database, including 39,346 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 0.70 (39346 hom., cov: 33)
• Consequence: SLC18A2 NM_003054.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.650
• Publications: 3 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=-0.96).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.821 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC18A2	NM_003054.6	c.991+1723C>T		intron_variant	Intron 10 of 15	ENST00000644641.2	NP_003045.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC18A2	ENST00000644641.2	c.991+1723C>T		intron_variant	Intron 10 of 15		NM_003054.6	ENSP00000496339.1
SLC18A2	ENST00000497497.1	n.1407+1723C>T		intron_variant	Intron 9 of 14	2

Frequencies

GnomAD3 genomes AF: 0.705 AC: 107142 AN: 152016 Hom.: 39351 Cov.: 33

Gnomad AFR AF: 0.519

Gnomad AMI AF: 0.763

Gnomad AMR AF: 0.700

Gnomad ASJ AF: 0.821

Gnomad EAS AF: 0.374

Gnomad SAS AF: 0.632

Gnomad FIN AF: 0.793

Gnomad MID AF: 0.850

Gnomad NFE AF: 0.827

Gnomad OTH AF: 0.729

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

GnomAD4 genome AF: 0.704 AC: 107148 AN: 152134 Hom.: 39346 Cov.: 33 AF XY: 0.699 AC XY: 51974 AN XY: 74354

African (AFR) AF: 0.518 AC: 21495 AN: 41464

American (AMR) AF: 0.700 AC: 10700 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.821 AC: 2852 AN: 3472

East Asian (EAS) AF: 0.374 AC: 1932 AN: 5170

South Asian (SAS) AF: 0.633 AC: 3049 AN: 4814

European-Finnish (FIN) AF: 0.793 AC: 8409 AN: 10606

Middle Eastern (MID) AF: 0.846 AC: 247 AN: 292

European-Non Finnish (NFE) AF: 0.827 AC: 56241 AN: 68010

Other (OTH) AF: 0.726 AC: 1530 AN: 2106

Alfa AF: 0.773 Hom.: 87389

Bravo AF: 0.687

Asia WGS AF: 0.474 AC: 1653 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.73
DANN	Benign	0.37
PhyloP100		-0.65
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: rs929493; hg19: chr10-119019126;