chr10-117241810-C-T

Variant names:

• chr10-117241810-C-T
• rs781006451
• NM_003054.6:c.117C>T

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 0P and 3B. BP4_Moderate BP7

The NM_003054.6(SLC18A2):​c.117C>T​(p.Val39Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000131 in 1,452,804 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. V39V) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.000013 (0 hom.)
• Consequence: SLC18A2 NM_003054.6 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.46
• Publications: 1 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: Likely_benign. The variant received -3 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.36).
• BP7: Synonymous conserved (PhyloP=-1.46 with no splicing effect.

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.117C>T	p.Val39Val	synonymous	Exon 2 of 16	NP_003045.2
	SLC18A2-AS1	NR_184309.1		n.113+75G>A		intron	N/A
	SLC18A2-AS1	NR_184310.1		n.114-27G>A		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC18A2	ENST00000644641.2	MANE Select	c.117C>T	p.Val39Val	synonymous	Exon 2 of 16	ENSP00000496339.1	Q05940-1
	SLC18A2	ENST00000853677.1		c.117C>T	p.Val39Val	synonymous	Exon 2 of 17	ENSP00000523736.1
	SLC18A2	ENST00000853679.1		c.117C>T	p.Val39Val	synonymous	Exon 2 of 17	ENSP00000523738.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.0000215 AC: 5 AN: 232614 AF XY: 0.0000392

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000131 AC: 19 AN: 1452804 Hom.: 0 Cov.: 33 AF XY: 0.0000194 AC XY: 14 AN XY: 722720

African (AFR) AF: 0.00 AC: 0 AN: 32272

American (AMR) AF: 0.00 AC: 0 AN: 44216

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25862

East Asian (EAS) AF: 0.00 AC: 0 AN: 38508

South Asian (SAS) AF: 0.000222 AC: 19 AN: 85706

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52316

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5276

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1108632

Other (OTH) AF: 0.00 AC: 0 AN: 60016

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.36
CADD	Benign	12
DANN	Benign	0.94
PhyloP100		-1.5

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs781006451; hg19: chr10-119001321;