NM_015061.6:c.698C>T

Variant names:

• chr9-6887978-C-T
• rs147868042
• NM_015061.6:c.698C>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_015061.6(KDM4C):​c.698C>T​(p.Ser233Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000549 in 1,458,256 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S233C) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000055 (0 hom.)
• Consequence: KDM4C NM_015061.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.08
• Publications: 4 publications found

Genes affected

KDM4C (HGNC:17071): (lysine demethylase 4C) This gene is a member of the Jumonji domain 2 (JMJD2) family. The encoded protein is a trimethylation-specific demethylase, and converts specific trimethylated histone residues to the dimethylated form. This enzymatic action regulates gene expression and chromosome segregation. Chromosomal aberrations and changes in expression of this gene may be found in tumor cells. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2015]

ACMG classification

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=0.0884994).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015061.6. 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
	KDM4C	NM_015061.6	MANE Select	c.698C>T	p.Ser233Phe	missense	Exon 7 of 22	NP_055876.2	Q9H3R0-1
	KDM4C	NM_001353997.3		c.698C>T	p.Ser233Phe	missense	Exon 7 of 23	NP_001340926.1
	KDM4C	NM_001304339.4		c.698C>T	p.Ser233Phe	missense	Exon 7 of 22	NP_001291268.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KDM4C	ENST00000381309.8	TSL:1 MANE Select	c.698C>T	p.Ser233Phe	missense	Exon 7 of 22	ENSP00000370710.3	Q9H3R0-1
	KDM4C	ENST00000536108.7	TSL:1	c.698C>T	p.Ser233Phe	missense	Exon 7 of 18	ENSP00000440656.4	Q9H3R0-3
	KDM4C	ENST00000948679.1		c.698C>T	p.Ser233Phe	missense	Exon 8 of 23	ENSP00000618738.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00 AC: 0 AN: 251200 AF XY: 0.00

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: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000549 AC: 8 AN: 1458256 Hom.: 0 Cov.: 27 AF XY: 0.00000551 AC XY: 4 AN XY: 725658

African (AFR) AF: 0.00 AC: 0 AN: 33392

American (AMR) AF: 0.00 AC: 0 AN: 44674

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26104

East Asian (EAS) AF: 0.00 AC: 0 AN: 39580

South Asian (SAS) AF: 0.00 AC: 0 AN: 86146

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53370

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5762

European-Non Finnish (NFE) AF: 0.00000721 AC: 8 AN: 1108980

Other (OTH) AF: 0.00 AC: 0 AN: 60248

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.10	T
BayesDel_noAF	Benign	-0.38
CADD	Benign	20
DANN	Benign	0.95
DEOGEN2	Benign	0.14	T
Eigen	Benign	-0.51
Eigen_PC	Benign	-0.29
FATHMM_MKL	Benign	0.55	D
LIST_S2	Benign	0.86	D
M_CAP	Benign	0.0086	T
MetaRNN	Benign	0.088	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	-0.42	N
PhyloP100		1.1
PrimateAI	Uncertain	0.58	T
PROVEAN	Benign	-2.1	N
REVEL	Benign	0.15
Sift	Uncertain	0.0090	D
Sift4G	Benign	0.71	T
Polyphen		0.019	B
Vest4		0.34
MutPred		0.58		Loss of disorder (P = 0.0122)
MVP		0.30
MPC		0.044
ClinPred		0.29	T
GERP RS		3.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Varity_R		0.24
gMVP		0.75
Mutation Taster		=75/25	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: rs147868042; hg19: chr9-6887978;