8-20180933-C-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_003053.4(SLC18A1):​c.32G>A​(p.Arg11Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000563 in 1,598,464 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000060 ( 0 hom. )

Consequence

SLC18A1
NM_003053.4 missense

Scores

1
18

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.20

Publications

4 publications found
Variant links:
Genes affected
SLC18A1 (HGNC:10934): (solute carrier family 18 member A1) The vesicular monoamine transporter acts to accumulate cytosolic monoamines into vesicles, using the proton gradient maintained across the vesicular membrane. Its proper function is essential to the correct activity of the monoaminergic systems that have been implicated in several human neuropsychiatric disorders. The transporter is a site of action of important drugs, including reserpine and tetrabenazine (Peter et al., 1993 [PubMed 7905859]). See also SLC18A2 (MIM 193001).[supplied by OMIM, Mar 2008]

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.041147977).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SLC18A1NM_003053.4 linkc.32G>A p.Arg11Gln missense_variant Exon 2 of 16 ENST00000276373.10 NP_003044.1 P54219-1Q96GL6

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
SLC18A1ENST00000276373.10 linkc.32G>A p.Arg11Gln missense_variant Exon 2 of 16 1 NM_003053.4 ENSP00000276373.5 P54219-1

Frequencies

GnomAD3 genomes
AF:
0.0000197
AC:
3
AN:
152188
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000241
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:
0.0000294
Gnomad OTH
AF:
0.00
GnomAD2 exomes
AF:
0.0000409
AC:
9
AN:
219958
AF XY:
0.0000592
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 FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000923
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000602
AC:
87
AN:
1446276
Hom.:
0
Cov.:
30
AF XY:
0.0000585
AC XY:
42
AN XY:
718100
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
33070
American (AMR)
AF:
0.00
AC:
0
AN:
41796
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
25926
East Asian (EAS)
AF:
0.00
AC:
0
AN:
38734
South Asian (SAS)
AF:
0.0000119
AC:
1
AN:
84092
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
52320
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
5748
European-Non Finnish (NFE)
AF:
0.0000778
AC:
86
AN:
1104710
Other (OTH)
AF:
0.00
AC:
0
AN:
59880
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.478
Heterozygous variant carriers
0
5
11
16
22
27
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Variant carriers
0
4
8
12
16
20
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome
AF:
0.0000197
AC:
3
AN:
152188
Hom.:
0
Cov.:
32
AF XY:
0.00
AC XY:
0
AN XY:
74352
show subpopulations
African (AFR)
AF:
0.0000241
AC:
1
AN:
41436
American (AMR)
AF:
0.00
AC:
0
AN:
15286
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
3472
East Asian (EAS)
AF:
0.00
AC:
0
AN:
5184
South Asian (SAS)
AF:
0.00
AC:
0
AN:
4830
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
10622
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
316
European-Non Finnish (NFE)
AF:
0.0000294
AC:
2
AN:
68036
Other (OTH)
AF:
0.00
AC:
0
AN:
2094
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.458
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Variant carriers
0
2
4
6
8
10
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
Alfa
AF:
0.00
Hom.:
0
Bravo
AF:
0.0000113
ExAC
AF:
0.0000330
AC:
4

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.069
BayesDel_addAF
Benign
-0.57
T
BayesDel_noAF
Benign
-0.86
CADD
Benign
1.7
DANN
Uncertain
0.98
DEOGEN2
Benign
0.036
.;T;T;.;.;.;.
Eigen
Benign
-1.2
Eigen_PC
Benign
-1.3
FATHMM_MKL
Benign
0.023
N
LIST_S2
Benign
0.68
.;.;T;T;T;.;T
M_CAP
Benign
0.0064
T
MetaRNN
Benign
0.041
T;T;T;T;T;T;T
MetaSVM
Benign
-0.91
T
MutationAssessor
Benign
0.91
L;L;L;L;L;L;.
PhyloP100
-2.2
PrimateAI
Benign
0.20
T
PROVEAN
Benign
0.18
N;N;N;N;N;N;N
REVEL
Benign
0.029
Sift
Benign
0.37
T;T;T;T;T;T;T
Sift4G
Benign
0.35
T;T;T;T;T;T;T
Polyphen
0.0030
.;B;B;.;.;.;.
Vest4
0.079
MutPred
0.14
Loss of MoRF binding (P = 0.0103);Loss of MoRF binding (P = 0.0103);Loss of MoRF binding (P = 0.0103);Loss of MoRF binding (P = 0.0103);Loss of MoRF binding (P = 0.0103);Loss of MoRF binding (P = 0.0103);Loss of MoRF binding (P = 0.0103);
MVP
0.067
MPC
0.0020
ClinPred
0.049
T
GERP RS
-4.3
PromoterAI
0.0088
Neutral
Varity_R
0.031
gMVP
0.24
Mutation Taster
=100/0
polymorphism

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.040
Details are displayed if max score is > 0.2

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

Publications

Other links and lift over

dbSNP: rs17092144; hg19: chr8-20038444; COSMIC: COSV52351463; API