10-117241742-C-T

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

Scores

9
10

Clinical Significance

Uncertain significance criteria provided, multiple submitters, no conflicts U:2

Conservation

PhyloP100: 4.35
Variant links:
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)

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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
SLC18A2NM_003054.6 linkuse as main transcriptc.49C>T p.Arg17Cys missense_variant 2/16 ENST00000644641.2 NP_003045.2
SLC18A2-AS1NR_184309.1 linkuse as main transcriptn.113+143G>A intron_variant, non_coding_transcript_variant
SLC18A2-AS1NR_184310.1 linkuse as main transcriptn.155G>A non_coding_transcript_exon_variant 2/3

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
SLC18A2ENST00000644641.2 linkuse as main transcriptc.49C>T p.Arg17Cys missense_variant 2/16 NM_003054.6 ENSP00000496339 P1Q05940-1
SLC18A2-AS1ENST00000425264.2 linkuse as main transcriptn.156G>A non_coding_transcript_exon_variant 2/33
SLC18A2ENST00000497497.1 linkuse as main transcriptn.192C>T non_coding_transcript_exon_variant 2/152
SLC18A2-AS1ENST00000691914.2 linkuse as main transcriptn.113+143G>A intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes
AF:
0.000296
AC:
45
AN:
152214
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.000121
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000588
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.000266
AC:
63
AN:
237006
Hom.:
0
AF XY:
0.000224
AC XY:
29
AN XY:
129536
show subpopulations
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 SAS exome
AF:
0.0000332
Gnomad FIN exome
AF:
0.0000481
Gnomad NFE exome
AF:
0.000577
Gnomad OTH exome
AF:
0.000173
GnomAD4 exome
AF:
0.000512
AC:
747
AN:
1457640
Hom.:
0
Cov.:
33
AF XY:
0.000452
AC XY:
328
AN XY:
724980
show subpopulations
Gnomad4 AFR exome
AF:
0.0000602
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000116
Gnomad4 FIN exome
AF:
0.000115
Gnomad4 NFE exome
AF:
0.000594
Gnomad4 OTH exome
AF:
0.00130
GnomAD4 genome
AF:
0.000296
AC:
45
AN:
152214
Hom.:
0
Cov.:
33
AF XY:
0.000242
AC XY:
18
AN XY:
74356
show subpopulations
Gnomad4 AFR
AF:
0.000121
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000588
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000363
Hom.:
0
Bravo
AF:
0.000332
ESP6500AA
AF:
0.000227
AC:
1
ESP6500EA
AF:
0.000698
AC:
6
ExAC
AF:
0.000365
AC:
44

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 submitterclinical testingAmbry GeneticsApr 26, 2023The 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 submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpAug 04, 2022This 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: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.10
BayesDel_addAF
Benign
-0.27
T
BayesDel_noAF
Benign
-0.27
CADD
Pathogenic
27
DANN
Uncertain
1.0
DEOGEN2
Benign
0.27
T;T
Eigen
Uncertain
0.26
Eigen_PC
Uncertain
0.36
FATHMM_MKL
Uncertain
0.94
D
LIST_S2
Uncertain
0.95
.;D
M_CAP
Uncertain
0.13
D
MetaRNN
Benign
0.13
T;T
MetaSVM
Uncertain
-0.088
T
MutationAssessor
Benign
1.5
L;L
MutationTaster
Benign
1.0
D
PrimateAI
Benign
0.36
T
PROVEAN
Benign
-1.8
N;.
REVEL
Uncertain
0.34
Sift
Benign
0.032
D;.
Sift4G
Uncertain
0.033
D;.
Polyphen
0.59
P;P
Vest4
0.25
MVP
0.45
MPC
0.67
ClinPred
0.19
T
GERP RS
5.2
Varity_R
0.25
gMVP
0.36

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs148348449; hg19: chr10-119001253; API