10-117241702-G-C

Variant names:

• chr10-117241702-G-C
• rs1589975966
• NM_003054.6:c.9G>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_003054.6(SLC18A2):​c.9G>C​(p.Leu3Leu) variant causes a synonymous change. The variant allele was found at a frequency of 0.000000693 in 1,443,800 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. L3L) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: SLC18A2 NM_003054.6 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.25
• Publications: 0 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-AS1 (HGNC:55843): (SLC18A2 antisense RNA 1)

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.32).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003054.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC18A2	NM_003054.6	MANE Select	c.9G>C	p.Leu3Leu	synonymous	Exon 2 of 16	NP_003045.2
	SLC18A2-AS1	NR_184310.1		n.195C>G		non_coding_transcript_exon	Exon 2 of 3
	SLC18A2-AS1	NR_184309.1		n.113+183C>G		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC18A2	ENST00000644641.2	MANE Select	c.9G>C	p.Leu3Leu	synonymous	Exon 2 of 16	ENSP00000496339.1	Q05940-1
	SLC18A2	ENST00000853677.1		c.9G>C	p.Leu3Leu	synonymous	Exon 2 of 17	ENSP00000523736.1
	SLC18A2	ENST00000853679.1		c.9G>C	p.Leu3Leu	synonymous	Exon 2 of 17	ENSP00000523738.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.93e-7 AC: 1 AN: 1443800 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 717010

African (AFR) AF: 0.00 AC: 0 AN: 32686

American (AMR) AF: 0.00 AC: 0 AN: 42564

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25632

East Asian (EAS) AF: 0.00 AC: 0 AN: 38644

South Asian (SAS) AF: 0.00 AC: 0 AN: 84262

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50848

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4760

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1104834

Other (OTH) AF: 0.0000168 AC: 1 AN: 59570

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.32
CADD	Benign	19
DANN	Benign	0.90
PhyloP100		5.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs1589975966; hg19: chr10-119001213;