chr1-6599318-C-T
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3
The NM_014851.4(KLHL21):c.1156G>A(p.Val386Met) variant causes a missense change. The variant allele was found at a frequency of 0.0000123 in 1,461,664 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 (★).
Frequency
Genomes: not found (cov: 33)
Exomes 𝑓: 0.000012 ( 0 hom. )
Consequence
KLHL21
NM_014851.4 missense
NM_014851.4 missense
Scores
9
7
3
Clinical Significance
Conservation
PhyloP100: 6.16
Genes affected
KLHL21 (HGNC:29041): (kelch like family member 21) Enables cullin family protein binding activity. Contributes to ubiquitin-protein transferase activity. Involved in chromosome passenger complex localization to spindle midzone; protein ubiquitination; and regulation of cytokinesis. Located in polar microtubule. Part of Cul3-RING ubiquitin ligase complex. [provided by Alliance of Genome Resources, Apr 2022]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 3 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
PP3
?
MetaRNN computational evidence supports a deleterious effect, 0.834
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
KLHL21 | NM_014851.4 | c.1156G>A | p.Val386Met | missense_variant | 2/4 | ENST00000377658.8 | |
KLHL21 | NM_001324309.2 | c.1156G>A | p.Val386Met | missense_variant | 2/4 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
KLHL21 | ENST00000377658.8 | c.1156G>A | p.Val386Met | missense_variant | 2/4 | 1 | NM_014851.4 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 33
GnomAD3 genomes
?
Cov.:
33
GnomAD3 exomes AF: 0.0000281 AC: 7AN: 249392Hom.: 0 AF XY: 0.0000148 AC XY: 2AN XY: 135078
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GnomAD4 exome AF: 0.0000123 AC: 18AN: 1461664Hom.: 0 Cov.: 30 AF XY: 0.00000963 AC XY: 7AN XY: 727118
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GnomAD4 genome ? Cov.: 33
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33
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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 | Jul 13, 2021 | The c.1156G>A (p.V386M) alteration is located in exon 2 (coding exon 2) of the KLHL21 gene. This alteration results from a G to A substitution at nucleotide position 1156, causing the valine (V) at amino acid position 386 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
Pathogenic
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
Cadd
Pathogenic
Dann
Pathogenic
DEOGEN2
Benign
T;.;T;T;.
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;D;D;D;D
M_CAP
Uncertain
D
MetaRNN
Pathogenic
D;D;D;D;D
MetaSVM
Pathogenic
D
MutationAssessor
Uncertain
M;M;.;.;.
MutationTaster
Benign
D;D;D;D
PrimateAI
Uncertain
T
PROVEAN
Benign
N;N;.;.;.
REVEL
Pathogenic
Sift
Uncertain
D;D;.;.;.
Sift4G
Uncertain
D;D;D;.;D
Polyphen
D;D;.;.;.
Vest4
MutPred
Gain of phosphorylation at Y385 (P = 0.1036);Gain of phosphorylation at Y385 (P = 0.1036);.;.;.;
MVP
MPC
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