NM_003054.6:c.28C>T

Variant names:

• chr10-117241721-C-T
• rs1017954648
• NM_003054.6:c.28C>T

Variant summary

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

The NM_003054.6(SLC18A2):​c.28C>T​(p.Arg10Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000688 in 1,452,712 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R10G) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: SLC18A2 NM_003054.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.940
• 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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC18A2	NM_003054.6	c.28C>T	p.Arg10Cys	missense_variant	Exon 2 of 16	ENST00000644641.2	NP_003045.2
SLC18A2-AS1	NR_184310.1	n.176G>A		non_coding_transcript_exon_variant	Exon 2 of 3
SLC18A2-AS1	NR_184309.1	n.113+164G>A		intron_variant	Intron 1 of 1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC18A2	ENST00000644641.2	c.28C>T	p.Arg10Cys	missense_variant	Exon 2 of 16		NM_003054.6	ENSP00000496339.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.88e-7 AC: 1 AN: 1452712 Hom.: 0 Cov.: 33 AF XY: 0.00000138 AC XY: 1 AN XY: 722116

African (AFR) AF: 0.00 AC: 0 AN: 33030

American (AMR) AF: 0.00 AC: 0 AN: 44000

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25856

East Asian (EAS) AF: 0.00 AC: 0 AN: 39176

South Asian (SAS) AF: 0.00 AC: 0 AN: 85182

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51480

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5118

European-Non Finnish (NFE) AF: 9.02e-7 AC: 1 AN: 1108882

Other (OTH) AF: 0.00 AC: 0 AN: 59988

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.20
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.45
CADD	Pathogenic	28
DANN	Uncertain	1.0
DEOGEN2	Benign	0.33	T;T
Eigen	Benign	0.14
Eigen_PC	Benign	0.13
FATHMM_MKL	Benign	0.61	D
LIST_S2	Uncertain	0.87	.;D
M_CAP	Benign	0.021	T
MetaRNN	Benign	0.36	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	2.0	M;M
PhyloP100		0.94
PrimateAI	Uncertain	0.62	T
PROVEAN	Benign	-1.7	N;.
REVEL	Benign	0.10
Sift	Uncertain	0.016	D;.
Sift4G	Uncertain	0.046	D;.
Polyphen		0.97	D;D
Vest4		0.58
MutPred		0.55		Gain of catalytic residue at W11 (P = 8e-04);Gain of catalytic residue at W11 (P = 8e-04);
MVP		0.068
MPC		0.73
ClinPred		0.78	D
GERP RS		1.8
Varity_R		0.13
gMVP		0.45
Mutation Taster		=91/9	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.26		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.26		Position offset: 12

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

Other links and lift over

dbSNP: rs1017954648; hg19: chr10-119001232; COSMIC: COSV53688687;