GeneBe

rs1392638187

Variant names:

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PM5PP3_Moderate

The NM_003054.6(SLC18A2):​c.1160C>A​(p.Pro387Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000707 in 1,414,152 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic 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. P387L) has been classified as Pathogenic.

Frequency

Genomes: not found (cov: 33)
Exomes 𝑓: 7.1e-7 ( 0 hom. )

Consequence

SLC18A2
NM_003054.6 missense

Scores

13
4
2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 7.78
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]

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ACMG classification

Classification made for transcript

Verdict is Likely_pathogenic. Variant got 6 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PM5
Other missense variant is known to change same aminoacid residue: Variant chr10-117267710-C-T is described in Lovd as [Pathogenic].
PP3
MetaRNN computational evidence supports a deleterious effect, 0.903

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SLC18A2NM_003054.6 linkc.1160C>A p.Pro387Gln missense_variant Exon 13 of 16 ENST00000644641.2 NP_003045.2 Q05940-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
SLC18A2ENST00000644641.2 linkc.1160C>A p.Pro387Gln missense_variant Exon 13 of 16 NM_003054.6 ENSP00000496339.1 Q05940-1
SLC18A2ENST00000497497.1 linkn.1576C>A non_coding_transcript_exon_variant Exon 12 of 15 2
ENSG00000277879ENST00000614747.1 linkn.959G>T non_coding_transcript_exon_variant Exon 1 of 1 6

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
AF:
7.07e-7
AC:
1
AN:
1414152
Hom.:
0
Cov.:
30
AF XY:
0.00
AC XY:
0
AN XY:
697856
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
9.30e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.95
BayesDel_addAF
Pathogenic
0.33
D
BayesDel_noAF
Pathogenic
0.24
CADD
Pathogenic
32
DANN
Uncertain
0.99
DEOGEN2
Uncertain
0.69
D;D
Eigen
Pathogenic
0.92
Eigen_PC
Pathogenic
0.87
FATHMM_MKL
Pathogenic
0.98
D
LIST_S2
Uncertain
0.95
.;D
M_CAP
Benign
0.052
D
MetaRNN
Pathogenic
0.90
D;D
MetaSVM
Uncertain
-0.032
T
MutationAssessor
Pathogenic
3.4
M;M
PrimateAI
Pathogenic
0.80
T
PROVEAN
Pathogenic
-7.4
D;.
REVEL
Pathogenic
0.66
Sift
Pathogenic
0.0
D;.
Sift4G
Pathogenic
0.0010
D;.
Polyphen
1.0
D;D
Vest4
0.91
MutPred
0.72
Loss of stability (P = 0.1142);Loss of stability (P = 0.1142);
MVP
0.63
MPC
1.0
ClinPred
1.0
D
GERP RS
5.6
Varity_R
0.86
gMVP
0.88

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr10-119027221; COSMIC: COSV100041245; API