11-95026067-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001161630.1(KDM4E):ā€‹c.510G>Cā€‹(p.Glu170Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000496 in 1,613,802 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: š‘“ 0.000020 ( 0 hom., cov: 31)
Exomes š‘“: 0.0000034 ( 0 hom. )

Consequence

KDM4E
NM_001161630.1 missense

Scores

3
16

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.0760
Variant links:
Genes affected
KDM4E (HGNC:37098): (lysine demethylase 4E) The protein encoded by this intronless gene is a member of a large family of histone lysine demethylases, which use oxygen and 2-oxoglutarate to demethylate di- and trimethylated lys9 of histone H3. Derepression of genes by demethylases is sometimes involved in viral infection or carcinogenesis, so inhibitors of these enzymes are desired. [provided by RefSeq, Dec 2016]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.10606229).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
KDM4ENM_001161630.1 linkuse as main transcriptc.510G>C p.Glu170Asp missense_variant 1/1 ENST00000450979.2 NP_001155102.1 B2RXH2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
KDM4EENST00000450979.2 linkuse as main transcriptc.510G>C p.Glu170Asp missense_variant 1/16 NM_001161630.1 ENSP00000397239.2 B2RXH2

Frequencies

GnomAD3 genomes
AF:
0.0000197
AC:
3
AN:
152136
Hom.:
0
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000196
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD4 exome
AF:
0.00000342
AC:
5
AN:
1461548
Hom.:
0
Cov.:
33
AF XY:
0.00000138
AC XY:
1
AN XY:
727094
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000180
Gnomad4 OTH exome
AF:
0.0000497
GnomAD4 genome
AF:
0.0000197
AC:
3
AN:
152254
Hom.:
0
Cov.:
31
AF XY:
0.0000134
AC XY:
1
AN XY:
74458
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.000196
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.00000378

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 submitterclinical testingAmbry GeneticsMay 14, 2024The c.510G>C (p.E170D) alteration is located in exon 1 (coding exon 1) of the KDM4E gene. This alteration results from a G to C substitution at nucleotide position 510, causing the glutamic acid (E) at amino acid position 170 to be replaced by an aspartic acid (D). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.27
BayesDel_addAF
Benign
-0.22
T
BayesDel_noAF
Benign
-0.55
CADD
Benign
13
DANN
Benign
0.93
DEOGEN2
Benign
0.067
T
Eigen
Benign
-1.3
Eigen_PC
Benign
-1.4
FATHMM_MKL
Benign
0.24
N
LIST_S2
Uncertain
0.87
D
M_CAP
Benign
0.016
T
MetaRNN
Benign
0.11
T
MetaSVM
Benign
-0.98
T
MutationAssessor
Benign
0.38
N
PrimateAI
Uncertain
0.69
T
PROVEAN
Uncertain
-2.6
D
REVEL
Benign
0.091
Sift
Benign
0.24
T
Sift4G
Benign
0.25
T
Polyphen
0.012
B
Vest4
0.060
MutPred
0.51
Loss of sheet (P = 0.1907);
MVP
0.043
MPC
0.34
ClinPred
0.051
T
GERP RS
-3.4
Varity_R
0.27
gMVP
0.25

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs555379365; hg19: chr11-94759231; API