dbSNP rs782516778: KDM4E:p.Gly81Asp (chr11-95025799-G-A) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001161630.1(KDM4E):c.242G>A(p.Gly81Asp) variant causes a missense change. The variant allele was found at a frequency of 0.00000347 in 1,439,472 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000035 ( 0 hom. )

Consequence

KDM4E
NM_001161630.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.98

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:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

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.242G>A	p.Gly81Asp	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.242G>A	p.Gly81Asp	missense	Exon 1 of 1	ENSP00000397239.2	B2RXH2
ENSG00000299693	ENST00000765628.1		n.192+11860C>T		intron	N/A
ENSG00000299693	ENST00000765629.1		n.175+11865C>T		intron	N/A

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.0000236

AC:

AN:

211782

AF XY:

0.00000865

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000125

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000103

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000347

AC:

AN:

1439472

Hom.:

Cov.:

AF XY:

0.00000140

AC XY:

AN XY:

715536

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32792

American (AMR)

AF:

0.0000920

AC:

AN:

43460

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25966

East Asian (EAS)

AF:

0.00

AC:

AN:

38976

South Asian (SAS)

AF:

0.00

AC:

AN:

84302

European-Finnish (FIN)

AF:

0.00

AC:

AN:

41852

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5758

European-Non Finnish (NFE)

AF:

9.04e-7

AC:

AN:

1106506

Other (OTH)

AF:

0.00

AC:

AN:

59860

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

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:

0.00

Hom.:

Bravo

AF:

0.00000756

ExAC

AF:

0.00000832

AC:

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

0.26

BayesDel_addAF

Benign

-0.078

BayesDel_noAF

Benign

-0.11

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.096

Eigen

Uncertain

0.50

Eigen_PC

Uncertain

0.28

FATHMM_MKL

Uncertain

0.94

LIST_S2

Pathogenic

0.99

M_CAP

Benign

0.0089

MetaRNN

Uncertain

0.71

MetaSVM

Uncertain

-0.18

MutationAssessor

Pathogenic

4.0

PhyloP100

7.0

PrimateAI

Uncertain

0.67

PROVEAN

Pathogenic

-6.7

REVEL

Benign

0.28

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0

Polyphen

1.0

Vest4

0.68

MutPred

0.47

Loss of catalytic residue at V82 (P = 0.0481)

MVP

0.043

MPC

1.3

ClinPred

0.99

GERP RS

2.2

Varity_R

0.84

gMVP

0.42

Mutation Taster

=67/33

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