dbSNP rs1555102694: KDM4E:p.Ile137Met (chr11-95025968-C-G) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001161630.1(KDM4E):c.411C>G(p.Ile137Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000209 in 1,433,592 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

KDM4E
NM_001161630.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.48

Publications

0 publications found

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]

KDM4E links:

ENSG00000299693 (HGNC:):

ENSG00000299693 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.14707121).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001161630.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KDM4E	NM_001161630.1	MANE Select	c.411C>G	p.Ile137Met	missense	Exon 1 of 1	NP_001155102.1	B2RXH2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
KDM4E	ENST00000450979.2	TSL:6 MANE Select	c.411C>G	p.Ile137Met	missense	Exon 1 of 1	ENSP00000397239.2	B2RXH2
ENSG00000299693	ENST00000765628.1		n.192+11691G>C		intron	N/A
ENSG00000299693	ENST00000765629.1		n.175+11696G>C		intron	N/A

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000506

AC:

AN:

197462

AF XY:

0.00000925

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000113

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000209

AC:

AN:

1433592

Hom.:

Cov.:

AF XY:

0.00000140

AC XY:

AN XY:

712414

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32608

American (AMR)

AF:

0.00

AC:

AN:

40864

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25884

East Asian (EAS)

AF:

0.00

AC:

AN:

38542

South Asian (SAS)

AF:

0.00

AC:

AN:

84612

European-Finnish (FIN)

AF:

0.00

AC:

AN:

44722

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5738

European-Non Finnish (NFE)

AF:

0.00000272

AC:

AN:

1100992

Other (OTH)

AF:

0.00

AC:

AN:

59630

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

Alfa

AF:

0.000111

Hom.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.17

BayesDel_addAF

Benign

-0.22

BayesDel_noAF

Benign

-0.55

CADD

Benign

(source)

DANN

Benign

0.62

DEOGEN2

Benign

0.033

Eigen

Benign

-0.74

Eigen_PC

Benign

-0.95

FATHMM_MKL

Benign

0.047

LIST_S2

Uncertain

0.95

M_CAP

Benign

0.0076

MetaRNN

Benign

0.15

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.2

PhyloP100

-1.5

PrimateAI

Uncertain

0.57

PROVEAN

Uncertain

-2.8

REVEL

Benign

0.049

Sift

Benign

0.12

Sift4G

Uncertain

0.0030

Polyphen

1.0

Vest4

0.19

MutPred

0.40

Loss of catalytic residue at I137 (P = 0.0222)

MVP

0.043

MPC

1.1

ClinPred

0.34

GERP RS

1.2

Varity_R

0.20

gMVP

0.19

Mutation Taster

=79/21

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over