11-63014739-G-A
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4
The NM_004254.4(SLC22A8):c.220C>T(p.Leu74Phe) variant causes a missense change. The variant allele was found at a frequency of 0.0000143 in 1,614,034 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 0.000020 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000014 ( 0 hom. )
Consequence
SLC22A8
NM_004254.4 missense
NM_004254.4 missense
Scores
10
8
Clinical Significance
Conservation
PhyloP100: 3.65
Genes affected
SLC22A8 (HGNC:10972): (solute carrier family 22 member 8) This gene encodes a protein involved in the sodium-independent transport and excretion of organic anions, some of which are potentially toxic. The encoded protein is an integral membrane protein and appears to be localized to the basolateral membrane of the kidney. Multiple alternatively spliced transcript variants that encode different protein isoforms have been described for this gene. [provided by RefSeq, May 2010]
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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=0.2980897).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SLC22A8 | NM_004254.4 | c.220C>T | p.Leu74Phe | missense_variant | 2/11 | ENST00000336232.7 | |
SLC22A8 | NM_001184732.2 | c.220C>T | p.Leu74Phe | missense_variant | 2/11 | ||
SLC22A8 | NM_001184733.2 | c.-25-29C>T | intron_variant | ||||
SLC22A8 | NM_001184736.2 | c.-37+990C>T | intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SLC22A8 | ENST00000336232.7 | c.220C>T | p.Leu74Phe | missense_variant | 2/11 | 1 | NM_004254.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000197 AC: 3AN: 152222Hom.: 0 Cov.: 33
GnomAD3 genomes
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GnomAD3 exomes AF: 0.0000199 AC: 5AN: 251454Hom.: 0 AF XY: 0.0000221 AC XY: 3AN XY: 135902
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GnomAD4 exome AF: 0.0000137 AC: 20AN: 1461812Hom.: 0 Cov.: 31 AF XY: 0.0000206 AC XY: 15AN XY: 727208
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GnomAD4 genome ? AF: 0.0000197 AC: 3AN: 152222Hom.: 0 Cov.: 33 AF XY: 0.0000134 AC XY: 1AN XY: 74362
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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 | Sep 23, 2023 | The c.220C>T (p.L74F) alteration is located in exon 2 (coding exon 1) of the SLC22A8 gene. This alteration results from a C to T substitution at nucleotide position 220, causing the leucine (L) at amino acid position 74 to be replaced by a phenylalanine (F). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Benign
Dann
Uncertain
DEOGEN2
Benign
T;T;T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
M_CAP
Uncertain
D
MetaRNN
Benign
T;T;T
MetaSVM
Uncertain
D
MutationAssessor
Uncertain
M;.;M
MutationTaster
Benign
D;D;D;D;D
PrimateAI
Benign
T
PROVEAN
Benign
N;N;N
REVEL
Uncertain
Sift
Uncertain
D;D;D
Sift4G
Uncertain
D;D;D
Polyphen
D;.;D
Vest4
MutPred
Loss of catalytic residue at L74 (P = 0.0475);Loss of catalytic residue at L74 (P = 0.0475);Loss of catalytic residue at L74 (P = 0.0475);
MVP
MPC
ClinPred
D
GERP RS
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