chr11-2909655-G-C
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Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate
The NM_002555.6(SLC22A18):āc.481G>Cā(p.Gly161Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000364 in 1,538,070 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ).
Frequency
Genomes: š 0.000020 ( 0 hom., cov: 33)
Exomes š: 0.000038 ( 0 hom. )
Consequence
SLC22A18
NM_002555.6 missense
NM_002555.6 missense
Scores
5
5
8
Clinical Significance
Conservation
PhyloP100: 2.37
Genes affected
SLC22A18 (HGNC:10964): (solute carrier family 22 member 18) This gene is one of several tumor-suppressing subtransferable fragments located in the imprinted gene domain of 11p15.5, an important tumor-suppressor gene region. Alterations in this region have been associated with the Beckwith-Wiedemann syndrome, Wilms tumor, rhabdomyosarcoma, adrenocortical carcinoma, and lung, ovarian, and breast cancer. This gene is imprinted, with preferential expression from the maternal allele. Mutations in this gene have been found in Wilms' tumor and lung cancer. This protein may act as a transporter of organic cations, and have a role in the transport of chloroquine and quinidine-related compounds in kidney. Several alternatively spliced transcript variants encoding different isoforms have been described. [provided by RefSeq, Oct 2015]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 4 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.932
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SLC22A18 | NM_002555.6 | c.481G>C | p.Gly161Arg | missense_variant | 5/11 | ENST00000649076.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SLC22A18 | ENST00000649076.2 | c.481G>C | p.Gly161Arg | missense_variant | 5/11 | NM_002555.6 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000197 AC: 3AN: 152080Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.00000755 AC: 1AN: 132528Hom.: 0 AF XY: 0.0000137 AC XY: 1AN XY: 73196
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GnomAD4 exome AF: 0.0000382 AC: 53AN: 1385872Hom.: 0 Cov.: 35 AF XY: 0.0000307 AC XY: 21AN XY: 684462
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GnomAD4 genome AF: 0.0000197 AC: 3AN: 152198Hom.: 0 Cov.: 33 AF XY: 0.0000269 AC XY: 2AN XY: 74410
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Dec 03, 2021 | The c.481G>C (p.G161R) alteration is located in exon 5 (coding exon 4) of the SLC22A18 gene. This alteration results from a G to C substitution at nucleotide position 481, causing the glycine (G) at amino acid position 161 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Uncertain
CADD
Uncertain
DANN
Uncertain
DEOGEN2
Benign
T;T;T;T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
D
M_CAP
Benign
D
MetaRNN
Pathogenic
D;D;D;D
MetaSVM
Benign
T
MutationAssessor
Uncertain
M;M;M;M
MutationTaster
Benign
N;N;N;N
PrimateAI
Pathogenic
D
PROVEAN
Pathogenic
D;D;.;D
REVEL
Uncertain
Sift
Uncertain
D;D;.;D
Sift4G
Benign
T;T;.;T
Polyphen
P;P;P;P
Vest4
MutPred
Gain of methylation at G161 (P = 0.0037);Gain of methylation at G161 (P = 0.0037);Gain of methylation at G161 (P = 0.0037);Gain of methylation at G161 (P = 0.0037);
MVP
MPC
0.77
ClinPred
D
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
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