11-95025886-C-T

Variant names:

• chr11-95025886-C-T
• rs182574403
• NM_001161630.1:c.329C>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_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. 13/22 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
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.95
• Publications: 3 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 -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.10411799).

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.329C>T	p.Pro110Leu	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.329C>T	p.Pro110Leu	missense	Exon 1 of 1	ENSP00000397239.2	B2RXH2
	ENSG00000299693	ENST00000765628.1		n.192+11773G>A		intron	N/A
	ENSG00000299693	ENST00000765629.1		n.175+11778G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.000729 AC: 111 AN: 152168 Hom.: 0 Cov.: 33

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

GnomAD2 exomes AF: 0.000362 AC: 76 AN: 209970 AF XY: 0.000339

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 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

African (AFR) AF: 0.000216 AC: 7 AN: 32470

American (AMR) AF: 0.0000467 AC: 2 AN: 42790

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26012

East Asian (EAS) AF: 0.0000521 AC: 2 AN: 38376

South Asian (SAS) AF: 0.00 AC: 0 AN: 84496

European-Finnish (FIN) AF: 0.000662 AC: 28 AN: 42276

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5756

European-Non Finnish (NFE) AF: 0.000538 AC: 595 AN: 1105630

Other (OTH) AF: 0.000402 AC: 24 AN: 59772

GnomAD4 genome AF: 0.000729 AC: 111 AN: 152284 Hom.: 0 Cov.: 33 AF XY: 0.000698 AC XY: 52 AN XY: 74462

African (AFR) AF: 0.000120 AC: 5 AN: 41522

American (AMR) AF: 0.00 AC: 0 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.00 AC: 0 AN: 4820

European-Finnish (FIN) AF: 0.000565 AC: 6 AN: 10624

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

European-Non Finnish (NFE) AF: 0.00144 AC: 98 AN: 68040

Other (OTH) AF: 0.000474 AC: 1 AN: 2110

Alfa AF: 0.00276 Hom.: 0

Bravo AF: 0.000382

ExAC AF: 0.000435 AC: 52

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	0.14
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
PhyloP100		3.0
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
Mutation Taster		=78/22	polymorphism

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

Other links and lift over

dbSNP: rs182574403; hg19: chr11-94759050; COSMIC: COSV71678344; COSMIC: COSV71678344;