10-117241742-C-T
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Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_003054.6(SLC18A2):c.49C>T(p.Arg17Cys) variant causes a missense change. The variant allele was found at a frequency of 0.000492 in 1,609,854 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).
Frequency
Genomes: 𝑓 0.00030 ( 0 hom., cov: 33)
Exomes 𝑓: 0.00051 ( 0 hom. )
Consequence
SLC18A2
NM_003054.6 missense
NM_003054.6 missense
Scores
9
10
Clinical Significance
Conservation
PhyloP100: 4.35
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]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 0 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.130317).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
SLC18A2 | NM_003054.6 | c.49C>T | p.Arg17Cys | missense_variant | 2/16 | ENST00000644641.2 | NP_003045.2 | |
SLC18A2-AS1 | NR_184309.1 | n.113+143G>A | intron_variant, non_coding_transcript_variant | |||||
SLC18A2-AS1 | NR_184310.1 | n.155G>A | non_coding_transcript_exon_variant | 2/3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
SLC18A2 | ENST00000644641.2 | c.49C>T | p.Arg17Cys | missense_variant | 2/16 | NM_003054.6 | ENSP00000496339 | P1 | ||
SLC18A2-AS1 | ENST00000425264.2 | n.156G>A | non_coding_transcript_exon_variant | 2/3 | 3 | |||||
SLC18A2 | ENST00000497497.1 | n.192C>T | non_coding_transcript_exon_variant | 2/15 | 2 | |||||
SLC18A2-AS1 | ENST00000691914.2 | n.113+143G>A | intron_variant, non_coding_transcript_variant |
Frequencies
GnomAD3 genomes AF: 0.000296 AC: 45AN: 152214Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.000266 AC: 63AN: 237006Hom.: 0 AF XY: 0.000224 AC XY: 29AN XY: 129536
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GnomAD4 exome AF: 0.000512 AC: 747AN: 1457640Hom.: 0 Cov.: 33 AF XY: 0.000452 AC XY: 328AN XY: 724980
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GnomAD4 genome AF: 0.000296 AC: 45AN: 152214Hom.: 0 Cov.: 33 AF XY: 0.000242 AC XY: 18AN XY: 74356
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Apr 26, 2023 | The c.49C>T (p.R17C) alteration is located in exon 2 (coding exon 1) of the SLC18A2 gene. This alteration results from a C to T substitution at nucleotide position 49, causing the arginine (R) at amino acid position 17 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Aug 04, 2022 | This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 17 of the SLC18A2 protein (p.Arg17Cys). This variant is present in population databases (rs148348449, gnomAD 0.05%). This variant has not been reported in the literature in individuals affected with SLC18A2-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Pathogenic
DANN
Uncertain
DEOGEN2
Benign
T;T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
.;D
M_CAP
Uncertain
D
MetaRNN
Benign
T;T
MetaSVM
Uncertain
T
MutationAssessor
Benign
L;L
MutationTaster
Benign
D
PrimateAI
Benign
T
PROVEAN
Benign
N;.
REVEL
Uncertain
Sift
Benign
D;.
Sift4G
Uncertain
D;.
Polyphen
P;P
Vest4
MVP
MPC
ClinPred
T
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Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at