10-117241726-G-C

Variant names:

• chr10-117241726-G-C
• NM_003054.6:c.33G>C
• SLC18A2 p.Trp11Cys

Variant summary

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

The NM_003054.6(SLC18A2):​c.33G>C​(p.Trp11Cys) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 33)
• Consequence: SLC18A2 NM_003054.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.94
• 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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.33G>C	p.Trp11Cys	missense	Exon 2 of 16	NP_003045.2
	SLC18A2-AS1	NR_184310.1		n.171C>G		non_coding_transcript_exon	Exon 2 of 3
	SLC18A2-AS1	NR_184309.1		n.113+159C>G		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC18A2	ENST00000644641.2	MANE Select	c.33G>C	p.Trp11Cys	missense	Exon 2 of 16	ENSP00000496339.1	Q05940-1
	SLC18A2	ENST00000853677.1		c.33G>C	p.Trp11Cys	missense	Exon 2 of 17	ENSP00000523736.1
	SLC18A2	ENST00000853679.1		c.33G>C	p.Trp11Cys	missense	Exon 2 of 17	ENSP00000523738.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.21
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.39
CADD	Pathogenic	32
DANN	Uncertain	0.98
DEOGEN2	Uncertain	0.47	T
Eigen	Benign	-0.015
Eigen_PC	Benign	0.14
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Benign	0.76	T
M_CAP	Benign	0.024	T
MetaRNN	Benign	0.36	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.7	L
PhyloP100		5.9
PrimateAI	Uncertain	0.60	T
PROVEAN	Uncertain	-4.2	D
REVEL	Benign	0.17
Sift	Benign	0.069	T
Sift4G	Benign	0.13	T
Varity_R		0.30
gMVP		0.77
Mutation Taster		=38/62	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.33		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.33		Position offset: 7

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr10-119001237;