chr6-160258487-G-A
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Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4
The NM_003058.4(SLC22A2):c.271C>T(p.Arg91Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000682 in 1,614,018 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 0.000092 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000066 ( 0 hom. )
Consequence
SLC22A2
NM_003058.4 missense
NM_003058.4 missense
Scores
3
8
8
Clinical Significance
Conservation
PhyloP100: 0.765
Genes affected
SLC22A2 (HGNC:10966): (solute carrier family 22 member 2) Polyspecific organic cation transporters in the liver, kidney, intestine, and other organs are critical for elimination of many endogenous small organic cations as well as a wide array of drugs and environmental toxins. This gene is one of three similar cation transporter genes located in a cluster on chromosome 6. The encoded protein contains twelve putative transmembrane domains and is a plasma integral membrane protein. It is found primarily in the kidney, where it may mediate the first step in cation reabsorption. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 1 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.35393548).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SLC22A2 | NM_003058.4 | c.271C>T | p.Arg91Cys | missense_variant | 1/11 | ENST00000366953.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SLC22A2 | ENST00000366953.8 | c.271C>T | p.Arg91Cys | missense_variant | 1/11 | 1 | NM_003058.4 | P1 | |
SLC22A2 | ENST00000366952.1 | c.208C>T | p.Arg70Cys | missense_variant | 3/8 | 5 | |||
SLC22A2 | ENST00000489644.1 | n.253C>T | non_coding_transcript_exon_variant | 1/2 | 3 | ||||
SLC22A2 | ENST00000491092.1 | n.272C>T | non_coding_transcript_exon_variant | 1/10 | 5 |
Frequencies
GnomAD3 genomes AF: 0.0000920 AC: 14AN: 152170Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.0000836 AC: 21AN: 251294Hom.: 0 AF XY: 0.0000663 AC XY: 9AN XY: 135848
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GnomAD4 exome AF: 0.0000657 AC: 96AN: 1461848Hom.: 0 Cov.: 32 AF XY: 0.0000619 AC XY: 45AN XY: 727238
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GnomAD4 genome AF: 0.0000920 AC: 14AN: 152170Hom.: 0 Cov.: 33 AF XY: 0.0000673 AC XY: 5AN XY: 74328
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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 19, 2022 | The c.271C>T (p.R91C) alteration is located in exon 1 (coding exon 1) of the SLC22A2 gene. This alteration results from a C to T substitution at nucleotide position 271, causing the arginine (R) at amino acid position 91 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Uncertain
DEOGEN2
Uncertain
D;T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
N
LIST_S2
Uncertain
D;D
M_CAP
Uncertain
D
MetaRNN
Benign
T;T
MetaSVM
Uncertain
T
MutationAssessor
Pathogenic
H;.
MutationTaster
Benign
N;N
PrimateAI
Benign
T
PROVEAN
Pathogenic
D;D
REVEL
Uncertain
Sift
Uncertain
D;D
Sift4G
Pathogenic
D;D
Polyphen
D;.
Vest4
MutPred
Loss of disorder (P = 0.0529);.;
MVP
MPC
ClinPred
D
GERP RS
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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