17-7845616-G-A
Variant summary
Our verdict is Likely benign. Variant got -1 ACMG points: 0P and 1B. BP4
The NM_001348716.2(KDM6B):c.62G>A(p.Gly21Asp) variant causes a missense change. The variant allele was found at a frequency of 0.0000564 in 1,614,062 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 0.000013 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000061 ( 0 hom. )
Consequence
KDM6B
NM_001348716.2 missense
NM_001348716.2 missense
Scores
1
7
10
Clinical Significance
Conservation
PhyloP100: 4.75
Genes affected
KDM6B (HGNC:29012): (lysine demethylase 6B) The protein encoded by this gene is a lysine-specific demethylase that specifically demethylates di- or tri-methylated lysine 27 of histone H3 (H3K27me2 or H3K27me3). H3K27 trimethylation is a repressive epigenetic mark controlling chromatin organization and gene silencing. This protein can also demethylate non-histone proteins such as retinoblastoma protein. Through its demethylation actvity this gene influences cellular differentiation and development, tumorigenesis, inflammatory diseases, and neurodegenerative diseases. This protein has two classical nuclear localization signals at its N-terminus. Alternative splicing results in multiple transcript variants encoding distinct isoforms. [provided by RefSeq, Feb 2017]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -1 ACMG points.
BP4
?
Computational evidence support a benign effect (MetaRNN=0.28964722).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
KDM6B | NM_001348716.2 | c.62G>A | p.Gly21Asp | missense_variant | 5/24 | ENST00000448097.7 | |
KDM6B | NM_001080424.2 | c.62G>A | p.Gly21Asp | missense_variant | 4/22 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
KDM6B | ENST00000448097.7 | c.62G>A | p.Gly21Asp | missense_variant | 5/24 | 5 | NM_001348716.2 | A2 | |
KDM6B | ENST00000254846.9 | c.62G>A | p.Gly21Asp | missense_variant | 4/22 | 1 | P2 | ||
KDM6B | ENST00000570632.1 | c.62G>A | p.Gly21Asp | missense_variant | 3/9 | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.0000131 AC: 2AN: 152242Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.00000798 AC: 2AN: 250658Hom.: 0 AF XY: 0.0000147 AC XY: 2AN XY: 135734
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GnomAD4 exome AF: 0.0000609 AC: 89AN: 1461820Hom.: 0 Cov.: 31 AF XY: 0.0000578 AC XY: 42AN XY: 727212
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Feb 01, 2024 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
BayesDel_addAF
Uncertain
T
BayesDel_noAF
Benign
Cadd
Pathogenic
Dann
Uncertain
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
T;T;T
M_CAP
Benign
T
MetaRNN
Benign
T;T;T
MetaSVM
Benign
T
MutationAssessor
Benign
N;N;.
MutationTaster
Benign
D;D
PrimateAI
Pathogenic
D
PROVEAN
Benign
N;N;.
REVEL
Benign
Sift
Benign
T;T;.
Sift4G
Uncertain
D;D;D
Polyphen
D;.;.
Vest4
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