8-20145870-G-A
Variant summary
Our verdict is Benign. Variant got -7 ACMG points: 0P and 7B. BP4_StrongBP6_ModerateBP7
The NM_003053.4(SLC18A1):c.1471C>T(p.Leu491=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000109 in 1,596,130 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).
Frequency
Genomes: 𝑓 0.000059 ( 0 hom., cov: 31)
Exomes 𝑓: 0.00011 ( 2 hom. )
Consequence
SLC18A1
NM_003053.4 synonymous
NM_003053.4 synonymous
Scores
4
11
Clinical Significance
Conservation
PhyloP100: 1.08
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]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -7 ACMG points.
BP4
?
Computational evidence support a benign effect (MetaRNN=0.01793757).
BP6
?
Variant 8-20145870-G-A is Benign according to our data. Variant chr8-20145870-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 3163218.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
Synonymous conserved (PhyloP=1.08 with no splicing effect.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SLC18A1 | NM_003053.4 | c.1471C>T | p.Leu491= | synonymous_variant | 16/16 | ENST00000276373.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SLC18A1 | ENST00000276373.10 | c.1471C>T | p.Leu491= | synonymous_variant | 16/16 | 1 | NM_003053.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000592 AC: 9AN: 152008Hom.: 0 Cov.: 31
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GnomAD3 exomes AF: 0.000208 AC: 50AN: 239950Hom.: 0 AF XY: 0.000262 AC XY: 34AN XY: 129944
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GnomAD4 exome AF: 0.000114 AC: 165AN: 1444004Hom.: 2 Cov.: 28 AF XY: 0.000164 AC XY: 118AN XY: 718648
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GnomAD4 genome ? AF: 0.0000592 AC: 9AN: 152126Hom.: 0 Cov.: 31 AF XY: 0.0000941 AC XY: 7AN XY: 74358
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Dec 12, 2023 | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Benign
Dann
Uncertain
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Benign
D
LIST_S2
Benign
T;.
M_CAP
Benign
T
MetaRNN
Benign
T;T
MetaSVM
Benign
T
MutationTaster
Benign
D;D;D;D;D;D
PROVEAN
Benign
N;N
REVEL
Benign
Sift
Uncertain
D;D
Sift4G
Benign
T;T
Vest4
MutPred
Loss of disorder (P = 0.0039);Loss of disorder (P = 0.0039);
MVP
ClinPred
T
GERP RS
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