rs553664971

Variant names:

• chr11-95025896-G-T
• rs553664971
• NM_001161630.1:c.339G>T

Your query was ambiguous. Multiple possible variants found:

• chr11-95025896-G-T
• chr11-95025896-G-A

Variant summary

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

The NM_001161630.1(KDM4E):​c.339G>T​(p.Gln113His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000347 in 1,585,106 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00020 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000017 (0 hom.)
• Consequence: KDM4E NM_001161630.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.92
• Publications: 2 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=0.011048496).

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.339G>T	p.Gln113His	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.339G>T	p.Gln113His	missense	Exon 1 of 1	ENSP00000397239.2	B2RXH2
	ENSG00000299693	ENST00000765628.1		n.192+11763C>A		intron	N/A
	ENSG00000299693	ENST00000765629.1		n.175+11768C>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.000197 AC: 30 AN: 152156 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000701

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000654

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000343 AC: 7 AN: 203964 AF XY: 0.0000357

Gnomad AFR exome AF: 0.000552

Gnomad AMR exome AF: 0.0000323

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000174 AC: 25 AN: 1432832 Hom.: 0 Cov.: 33 AF XY: 0.0000183 AC XY: 13 AN XY: 711824

African (AFR) AF: 0.000525 AC: 17 AN: 32374

American (AMR) AF: 0.00 AC: 0 AN: 41968

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25958

East Asian (EAS) AF: 0.00 AC: 0 AN: 37996

South Asian (SAS) AF: 0.00 AC: 0 AN: 84042

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 41852

Middle Eastern (MID) AF: 0.000695 AC: 4 AN: 5752

European-Non Finnish (NFE) AF: 9.06e-7 AC: 1 AN: 1103280

Other (OTH) AF: 0.0000503 AC: 3 AN: 59610

GnomAD4 genome AF: 0.000197 AC: 30 AN: 152274 Hom.: 0 Cov.: 32 AF XY: 0.000201 AC XY: 15 AN XY: 74462

African (AFR) AF: 0.000698 AC: 29 AN: 41520

American (AMR) AF: 0.0000653 AC: 1 AN: 15308

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5192

South Asian (SAS) AF: 0.00 AC: 0 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10614

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68030

Other (OTH) AF: 0.00 AC: 0 AN: 2112

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.000200

ExAC AF: 0.0000504 AC: 6

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	0.11
BayesDel_addAF	Benign	-0.34	T
BayesDel_noAF	Benign	-0.73
CADD	Benign	0.86
DANN	Benign	0.56
DEOGEN2	Benign	0.011	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.016	N
LIST_S2	Benign	0.099	T
M_CAP	Benign	0.0061	T
MetaRNN	Benign	0.011	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.1	M
PhyloP100		-1.9
PrimateAI	Benign	0.29	T
PROVEAN	Uncertain	-2.9	D
REVEL	Benign	0.012
Sift	Benign	0.40	T
Sift4G	Benign	0.12	T
Polyphen		0.035	B
Vest4		0.046
MutPred		0.32		Gain of catalytic residue at N114 (P = 0.1127)
MVP		0.082
MPC		0.33
ClinPred		0.024	T
GERP RS		-1.6
Varity_R		0.10
gMVP		0.24
Mutation Taster		=92/8	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.11		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: rs553664971; hg19: chr11-94759060;