19-5032945-C-T
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Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2
The NM_015015.3(KDM4B):c.55C>T(p.Arg19Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000157 in 1,461,854 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.0 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000016 ( 0 hom. )
Failed GnomAD Quality Control
Consequence
KDM4B
NM_015015.3 missense
NM_015015.3 missense
Scores
4
9
6
Clinical Significance
Conservation
PhyloP100: 2.74
Genes affected
KDM4B (HGNC:29136): (lysine demethylase 4B) Enables histone H3-methyl-lysine-36 demethylase activity and histone H3-methyl-lysine-9 demethylase activity. Involved in histone H3-K36 demethylation and histone H3-K9 demethylation. Located in cytosol and nucleoplasm. Implicated in autosomal dominant non-syndromic intellectual disability; breast cancer; colorectal cancer; malignant peripheral nerve sheath tumor; and stomach cancer. Biomarker of several diseases, including alopecia areata; lung cancer; medulloblastoma; prostate cancer; and stomach cancer. [provided by Alliance of Genome Resources, Apr 2022]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -4 ACMG points.
BS2
High AC in GnomAdExome4 at 23 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
KDM4B | NM_015015.3 | c.55C>T | p.Arg19Cys | missense_variant | 3/23 | ENST00000159111.9 | NP_055830.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
KDM4B | ENST00000159111.9 | c.55C>T | p.Arg19Cys | missense_variant | 3/23 | 1 | NM_015015.3 | ENSP00000159111.3 |
Frequencies
GnomAD3 genomes AF: 0.00 AC: 0AN: 152222Hom.: 0 Cov.: 33 FAILED QC
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GnomAD3 exomes AF: 0.00000795 AC: 2AN: 251442Hom.: 0 AF XY: 0.0000147 AC XY: 2AN XY: 135900
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GnomAD4 exome AF: 0.0000157 AC: 23AN: 1461854Hom.: 0 Cov.: 31 AF XY: 0.0000179 AC XY: 13AN XY: 727222
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GnomAD4 genome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0AN: 152222Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0AN XY: 74364
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
KDM4B-related disorder Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Sep 05, 2023 | The KDM4B c.55C>T variant is predicted to result in the amino acid substitution p.Arg19Cys. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.0029% of alleles in individuals of Latino descent in gnomAD (http://gnomad.broadinstitute.org/variant/19-5032956-C-T). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Uncertain
CADD
Pathogenic
DANN
Pathogenic
DEOGEN2
Benign
T;.;T;.;T
Eigen
Uncertain
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;D;D;D;.
M_CAP
Benign
T
MetaRNN
Uncertain
D;D;D;D;D
MetaSVM
Benign
T
MutationAssessor
Pathogenic
.;.;.;M;.
PrimateAI
Uncertain
T
PROVEAN
Pathogenic
.;.;D;D;D
REVEL
Uncertain
Sift
Uncertain
.;.;D;D;D
Sift4G
Uncertain
D;D;D;D;D
Polyphen
D;.;.;P;D
Vest4
MutPred
Gain of catalytic residue at T21 (P = 0.0449);Gain of catalytic residue at T21 (P = 0.0449);Gain of catalytic residue at T21 (P = 0.0449);Gain of catalytic residue at T21 (P = 0.0449);Gain of catalytic residue at T21 (P = 0.0449);
MVP
MPC
2.9
ClinPred
D
GERP RS
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