12-293103-G-A
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PP2PP3
The NM_001042603.3(KDM5A):c.4522C>T(p.Arg1508Trp) variant causes a missense change. The variant allele was found at a frequency of 0.0000132 in 1,595,926 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 not provided (no stars).
Frequency
Genomes: 𝑓 0.000020 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000012 ( 0 hom. )
Consequence
KDM5A
NM_001042603.3 missense
NM_001042603.3 missense
Scores
12
6
1
Clinical Significance
Conservation
PhyloP100: 5.26
Genes affected
KDM5A (HGNC:9886): (lysine demethylase 5A) This gene encodes a member of the Jumonji, AT-rich interactive domain 1 (JARID1) histone demethylase protein family. The encoded protein plays a role in gene regulation through the histone code by specifically demethylating lysine 4 of histone H3. The encoded protein interacts with many other proteins, including retinoblastoma protein, and is implicated in the transcriptional regulation of Hox genes and cytokines. This gene may play a role in tumor progression. [provided by RefSeq, Aug 2013]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 2 ACMG points.
PP2
?
Missense variant where missense usually causes diseases, KDM5A
PP3
?
MetaRNN computational evidence supports a deleterious effect, 0.822
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
KDM5A | NM_001042603.3 | c.4522C>T | p.Arg1508Trp | missense_variant | 27/28 | ENST00000399788.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
KDM5A | ENST00000399788.7 | c.4522C>T | p.Arg1508Trp | missense_variant | 27/28 | 1 | NM_001042603.3 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000197 AC: 3AN: 152058Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000130 AC: 3AN: 230760Hom.: 0 AF XY: 0.0000160 AC XY: 2AN XY: 125244
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GnomAD4 exome AF: 0.0000125 AC: 18AN: 1443868Hom.: 0 Cov.: 32 AF XY: 0.00000697 AC XY: 5AN XY: 717778
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GnomAD4 genome ? AF: 0.0000197 AC: 3AN: 152058Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74272
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ClinVar
Significance: not provided
Submissions summary: Other:1
Revision: no classification provided
LINK: link
Submissions by phenotype
not provided Other:1
not provided, no classification provided | literature only | Richard Lifton Laboratory, Yale University School of Medicine | - | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Uncertain
Cadd
Pathogenic
Dann
Pathogenic
DEOGEN2
Uncertain
D
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
LIST_S2
Pathogenic
D
M_CAP
Pathogenic
D
MetaRNN
Pathogenic
D
MetaSVM
Uncertain
D
MutationAssessor
Uncertain
M
MutationTaster
Benign
D;D
PrimateAI
Uncertain
T
PROVEAN
Pathogenic
D
REVEL
Uncertain
Sift
Pathogenic
D
Sift4G
Pathogenic
D
Polyphen
D
Vest4
MVP
MPC
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
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Calibrated prediction
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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