chr1-202729907-G-T
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_006618.5(KDM5B):c.4297C>A(p.Pro1433Thr) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,461,864 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000014 ( 0 hom. )
Consequence
KDM5B
NM_006618.5 missense
NM_006618.5 missense
Scores
1
11
7
Clinical Significance
Conservation
PhyloP100: 5.76
Genes affected
KDM5B (HGNC:18039): (lysine demethylase 5B) This gene encodes a lysine-specific histone demethylase that belongs to the jumonji/ARID domain-containing family of histone demethylases. The encoded protein is capable of demethylating tri-, di- and monomethylated lysine 4 of histone H3. This protein plays a role in the transcriptional repression or certain tumor suppressor genes and is upregulated in certain cancer cells. This protein may also play a role in genome stability and DNA repair. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Nov 2016]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 2 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
KDM5B | NM_006618.5 | c.4297C>A | p.Pro1433Thr | missense_variant | 26/27 | ENST00000367265.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
KDM5B | ENST00000367265.9 | c.4297C>A | p.Pro1433Thr | missense_variant | 26/27 | 1 | NM_006618.5 | P4 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
Cov.:
32
GnomAD4 exome AF: 0.00000137 AC: 2AN: 1461864Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0AN XY: 727234
GnomAD4 exome
AF:
AC:
2
AN:
1461864
Hom.:
Cov.:
31
AF XY:
AC XY:
0
AN XY:
727234
Gnomad4 AFR exome
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GnomAD4 genome ? Cov.: 32
GnomAD4 genome
?
Cov.:
32
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | May 18, 2021 | The c.4297C>A (p.P1433T) alteration is located in exon 26 (coding exon 26) of the KDM5B gene. This alteration results from a C to A substitution at nucleotide position 4297, causing the proline (P) at amino acid position 1433 to be replaced by a threonine (T). 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
Uncertain
D
BayesDel_noAF
Benign
Cadd
Uncertain
Dann
Uncertain
DEOGEN2
Benign
T;.;.;.;.;.;.;.;.
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D;D;D;D;D;D;D;D;T
M_CAP
Benign
D
MetaRNN
Uncertain
T;T;T;T;T;T;T;T;D
MetaSVM
Uncertain
D
MutationAssessor
Benign
L;.;.;.;.;.;.;.;.
MutationTaster
Benign
D;D
PrimateAI
Uncertain
T
PROVEAN
Uncertain
N;.;N;.;.;.;.;.;N
REVEL
Uncertain
Sift
Benign
T;.;T;.;.;.;.;.;D
Sift4G
Uncertain
T;.;T;.;.;.;.;.;D
Polyphen
P;.;P;.;.;.;.;.;.
Vest4
MutPred
Gain of phosphorylation at P1433 (P = 0.0086);Gain of phosphorylation at P1433 (P = 0.0086);.;.;Gain of phosphorylation at P1433 (P = 0.0086);.;.;.;.;
MVP
MPC
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
No publications associated with this variant yet.