rs568507965

Variant names:

• chr11-95025853-G-A
• rs568507965
• NM_001161630.1:c.296G>A

Your query was ambiguous. Multiple possible variants found:

• chr11-95025853-G-A
• chr11-95025853-G-C
• chr11-95025853-G-T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001161630.1(KDM4E):​c.296G>A​(p.Arg99His) variant causes a missense change. The variant allele was found at a frequency of 0.000067 in 1,595,894 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 (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R99C) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.00026 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000046 (0 hom.)
• Consequence: KDM4E NM_001161630.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.02
• Publications: 0 publications found

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]

ENSG00000299693 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.013653576).

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.296G>A	p.Arg99His	missense	Exon 1 of 1	NP_001155102.1	B2RXH2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KDM4E	ENST00000450979.2	TSL:6 MANE Select	c.296G>A	p.Arg99His	missense	Exon 1 of 1	ENSP00000397239.2	B2RXH2
	ENSG00000299693	ENST00000765628.1		n.192+11806C>T		intron	N/A
	ENSG00000299693	ENST00000765629.1		n.175+11811C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.000263 AC: 40 AN: 152230 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.000820

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000131

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000576

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.000478

GnomAD2 exomes AF: 0.000106 AC: 24 AN: 227258 AF XY: 0.0000885

Gnomad AFR exome AF: 0.000914

Gnomad AMR exome AF: 0.0000598

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000355

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000379

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000464 AC: 67 AN: 1443546 Hom.: 0 Cov.: 35 AF XY: 0.0000529 AC XY: 38 AN XY: 717972

African (AFR) AF: 0.000733 AC: 24 AN: 32738

American (AMR) AF: 0.0000685 AC: 3 AN: 43826

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26056

East Asian (EAS) AF: 0.000205 AC: 8 AN: 39020

South Asian (SAS) AF: 0.0000117 AC: 1 AN: 85132

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 42404

Middle Eastern (MID) AF: 0.000174 AC: 1 AN: 5760

European-Non Finnish (NFE) AF: 0.0000244 AC: 27 AN: 1108588

Other (OTH) AF: 0.0000500 AC: 3 AN: 60022

GnomAD4 genome AF: 0.000263 AC: 40 AN: 152348 Hom.: 0 Cov.: 33 AF XY: 0.000309 AC XY: 23 AN XY: 74502

African (AFR) AF: 0.000818 AC: 34 AN: 41562

American (AMR) AF: 0.000131 AC: 2 AN: 15310

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.000578 AC: 3 AN: 5194

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10620

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68038

Other (OTH) AF: 0.000473 AC: 1 AN: 2116

Alfa AF: 0.0000434 Hom.: 0

Bravo AF: 0.000329

ExAC AF: 0.0000830 AC: 10

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.094
BayesDel_addAF	Benign	-0.50	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	11
DANN	Benign	0.87
DEOGEN2	Benign	0.043	T
Eigen	Benign	-0.79
Eigen_PC	Benign	-0.90
FATHMM_MKL	Uncertain	0.81	D
LIST_S2	Uncertain	0.86	D
M_CAP	Benign	0.0064	T
MetaRNN	Benign	0.014	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Uncertain	2.2	M
PhyloP100		4.0
PrimateAI	Benign	0.39	T
PROVEAN	Uncertain	-4.2	D
REVEL	Benign	0.13
Sift	Benign	0.091	T
Sift4G	Uncertain	0.027	D
Polyphen		0.26	B
Vest4		0.080
MVP		0.10
MPC		0.44
ClinPred		0.060	T
GERP RS		0.25
Varity_R		0.090
gMVP		0.25
Mutation Taster		=67/33	polymorphism

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

Other links and lift over

dbSNP: rs568507965; hg19: chr11-94759017; COSMIC: COSV108261748; COSMIC: COSV108261748;