NM_001161630.1:c.329C>T

Variant summary

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

The NM_001161630.1(KDM4E):​c.329C>T​(p.Pro110Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000484 in 1,589,862 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00073 ( 0 hom., cov: 33)
Exomes 𝑓: 0.00046 ( 0 hom. )

Consequence

KDM4E
NM_001161630.1 missense

Scores

4
5
10

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.95
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=0.10411799).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
KDM4ENM_001161630.1 linkc.329C>T p.Pro110Leu missense_variant Exon 1 of 1 ENST00000450979.2 NP_001155102.1 B2RXH2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
KDM4EENST00000450979.2 linkc.329C>T p.Pro110Leu missense_variant Exon 1 of 1 6 NM_001161630.1 ENSP00000397239.2 B2RXH2

Frequencies

GnomAD3 genomes
AF:
0.000729
AC:
111
AN:
152168
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.000121
Gnomad AMI
AF:
0.00110
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.000565
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00144
Gnomad OTH
AF:
0.000479
GnomAD3 exomes
AF:
0.000362
AC:
76
AN:
209970
Hom.:
0
AF XY:
0.000339
AC XY:
39
AN XY:
115096
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000946
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.0000654
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.000422
Gnomad NFE exome
AF:
0.000653
Gnomad OTH exome
AF:
0.000730
GnomAD4 exome
AF:
0.000458
AC:
658
AN:
1437578
Hom.:
0
Cov.:
35
AF XY:
0.000487
AC XY:
348
AN XY:
714620
show subpopulations
Gnomad4 AFR exome
AF:
0.000216
Gnomad4 AMR exome
AF:
0.0000467
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000521
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.000662
Gnomad4 NFE exome
AF:
0.000538
Gnomad4 OTH exome
AF:
0.000402
GnomAD4 genome
AF:
0.000729
AC:
111
AN:
152284
Hom.:
0
Cov.:
33
AF XY:
0.000698
AC XY:
52
AN XY:
74462
show subpopulations
Gnomad4 AFR
AF:
0.000120
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.000565
Gnomad4 NFE
AF:
0.00144
Gnomad4 OTH
AF:
0.000474
Alfa
AF:
0.00276
Hom.:
0
Bravo
AF:
0.000382
ExAC
AF:
0.000435
AC:
52

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Oct 04, 2022
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.329C>T (p.P110L) alteration is located in exon 1 (coding exon 1) of the KDM4E gene. This alteration results from a C to T substitution at nucleotide position 329, causing the proline (P) at amino acid position 110 to be replaced by a leucine (L). 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
0.14
BayesDel_addAF
Benign
-0.26
T
BayesDel_noAF
Benign
-0.25
CADD
Benign
21
DANN
Uncertain
1.0
DEOGEN2
Benign
0.068
T
Eigen
Uncertain
0.27
Eigen_PC
Benign
0.016
FATHMM_MKL
Uncertain
0.94
D
LIST_S2
Uncertain
0.93
D
M_CAP
Benign
0.025
D
MetaRNN
Benign
0.10
T
MetaSVM
Uncertain
-0.14
T
MutationAssessor
Pathogenic
3.6
H
PrimateAI
Benign
0.43
T
PROVEAN
Pathogenic
-9.7
D
REVEL
Benign
0.23
Sift
Pathogenic
0.0
D
Sift4G
Pathogenic
0.0
D
Polyphen
1.0
D
Vest4
0.28
MVP
0.13
MPC
1.1
ClinPred
0.98
D
GERP RS
2.7
Varity_R
0.44
gMVP
0.31

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.020
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: rs182574403; hg19: chr11-94759050; COSMIC: COSV71678344; COSMIC: COSV71678344; API