2-23642406-G-A
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Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 3P and 2B. PM2PP2BP4_Moderate
The NM_052920.2(KLHL29):c.496G>A(p.Val166Met) variant causes a missense change. The variant allele was found at a frequency of 0.0000182 in 1,481,940 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000059 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000014 ( 0 hom. )
Consequence
KLHL29
NM_052920.2 missense
NM_052920.2 missense
Scores
3
16
Clinical Significance
Conservation
PhyloP100: 3.64
Genes affected
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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;
PP2
Missense variant where missense usually causes diseases, KLHL29
BP4
Computational evidence support a benign effect (MetaRNN=0.07927948).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
KLHL29 | NM_052920.2 | c.496G>A | p.Val166Met | missense_variant | 5/14 | ENST00000486442.6 | |
KLHL29 | XM_006711929.4 | c.496G>A | p.Val166Met | missense_variant | 4/13 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
KLHL29 | ENST00000486442.6 | c.496G>A | p.Val166Met | missense_variant | 5/14 | 5 | NM_052920.2 | P1 | |
KLHL29 | ENST00000288548.5 | c.16G>A | p.Val6Met | missense_variant | 1/7 | 1 | |||
KLHL29 | ENST00000489446.1 | n.577G>A | non_coding_transcript_exon_variant | 4/4 | 1 |
Frequencies
GnomAD3 genomes AF: 0.0000591 AC: 9AN: 152242Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.00000949 AC: 1AN: 105326Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 52786
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GnomAD4 exome AF: 0.0000135 AC: 18AN: 1329698Hom.: 0 Cov.: 36 AF XY: 0.00000928 AC XY: 6AN XY: 646782
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GnomAD4 genome AF: 0.0000591 AC: 9AN: 152242Hom.: 0 Cov.: 33 AF XY: 0.0000807 AC XY: 6AN XY: 74380
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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 | Nov 18, 2022 | The c.496G>A (p.V166M) alteration is located in exon 5 (coding exon 3) of the KLHL29 gene. This alteration results from a G to A substitution at nucleotide position 496, causing the valine (V) at amino acid position 166 to be replaced by a methionine (M). 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
Benign
DEOGEN2
Benign
T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D
M_CAP
Benign
T
MetaRNN
Benign
T
MetaSVM
Benign
T
MutationAssessor
Benign
N
MutationTaster
Benign
D
PrimateAI
Uncertain
T
PROVEAN
Benign
N
REVEL
Benign
Sift
Benign
T
Sift4G
Benign
T
Vest4
MVP
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