chr14-20428973-C-T
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Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_001365790.2(KLHL33):c.2270G>A(p.Arg757Gln) variant causes a missense change. The variant allele was found at a frequency of 0.0000606 in 1,551,676 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 0.00012 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000054 ( 0 hom. )
Consequence
KLHL33
NM_001365790.2 missense
NM_001365790.2 missense
Scores
1
5
8
Clinical Significance
Conservation
PhyloP100: 5.94
Genes affected
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 0 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.2224997).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
KLHL33 | NM_001365790.2 | c.2270G>A | p.Arg757Gln | missense_variant | 5/5 | ENST00000636854.3 | |
KLHL33 | NM_001109997.3 | c.1478G>A | p.Arg493Gln | missense_variant | 4/4 | ||
KLHL33 | XM_011536450.3 | c.2270G>A | p.Arg757Gln | missense_variant | 5/5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
KLHL33 | ENST00000636854.3 | c.2270G>A | p.Arg757Gln | missense_variant | 5/5 | 5 | NM_001365790.2 | P1 | |
KLHL33 | ENST00000344581.4 | c.1478G>A | p.Arg493Gln | missense_variant | 4/4 | 5 | |||
KLHL33 | ENST00000637228.1 | c.*429G>A | 3_prime_UTR_variant | 4/4 | 5 |
Frequencies
GnomAD3 genomes AF: 0.000125 AC: 19AN: 152160Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.0000704 AC: 11AN: 156224Hom.: 0 AF XY: 0.0000483 AC XY: 4AN XY: 82806
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GnomAD4 exome AF: 0.0000536 AC: 75AN: 1399398Hom.: 0 Cov.: 37 AF XY: 0.0000507 AC XY: 35AN XY: 690200
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GnomAD4 genome AF: 0.000125 AC: 19AN: 152278Hom.: 0 Cov.: 33 AF XY: 0.000134 AC XY: 10AN XY: 74458
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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 16, 2021 | The c.1478G>A (p.R493Q) alteration is located in exon 4 (coding exon 3) of the KLHL33 gene. This alteration results from a G to A substitution at nucleotide position 1478, causing the arginine (R) at amino acid position 493 to be replaced by a glutamine (Q). 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
Uncertain
DANN
Pathogenic
DEOGEN2
Benign
T;T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;D
M_CAP
Benign
T
MetaRNN
Benign
T;T
MetaSVM
Benign
T
MutationTaster
Benign
D
PrimateAI
Uncertain
T
Polyphen
1.0
.;D
Vest4
0.39
MVP
0.17
ClinPred
T
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