chr9-7174673-G-T

Variant names:

• chr9-7174673-G-T
• rs913588
• NM_015061.6:c.3115G>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_015061.6(KDM4C):​c.3115G>T​(p.Val1039Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: KDM4C NM_015061.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.15
• Publications: 61 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.056886137).

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.3115G>T	p.Val1039Leu	missense	Exon 22 of 22	NP_055876.2	Q9H3R0-1
	KDM4C	NM_001353997.3		c.3214G>T	p.Val1072Leu	missense	Exon 23 of 23	NP_001340926.1
	KDM4C	NM_001304340.4		c.2350G>T	p.Val784Leu	missense	Exon 20 of 20	NP_001291269.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KDM4C	ENST00000381309.8	TSL:1 MANE Select	c.3115G>T	p.Val1039Leu	missense	Exon 22 of 22	ENSP00000370710.3	Q9H3R0-1
	KDM4C	ENST00000948679.1		c.3115G>T	p.Val1039Leu	missense	Exon 23 of 23	ENSP00000618738.1
	KDM4C	ENST00000948683.1		c.3115G>T	p.Val1039Leu	missense	Exon 22 of 22	ENSP00000618742.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 40

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 79496

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.56
CADD	Benign	17
DANN	Benign	0.95
DEOGEN2	Benign	0.0044	T
Eigen	Benign	-0.46
Eigen_PC	Benign	-0.21
FATHMM_MKL	Benign	0.69	D
LIST_S2	Benign	0.84	T
M_CAP	Benign	0.0026	T
MetaRNN	Benign	0.057	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.34	N
PhyloP100		3.2
PrimateAI	Uncertain	0.58	T
PROVEAN	Benign	-0.090	N
REVEL	Benign	0.030
Sift	Benign	0.44	T
Sift4G	Benign	0.41	T
Polyphen		0.0010	B
Vest4		0.077
MutPred		0.20		Loss of MoRF binding (P = 0.0923)
MVP		0.22
MPC		0.040
ClinPred		0.70	D
GERP RS		4.7
Varity_R		0.060
gMVP		0.29
Mutation Taster		=95/5	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs913588; hg19: chr9-7174673;