9-6849689-G-A

Variant names:

• chr9-6849689-G-A
• rs7864351
• NM_015061.6:c.618G>A

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 2P and 3B. PM2 BP4_Moderate BP7

The NM_015061.6(KDM4C):​c.618G>A​(p.Glu206Glu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000071 in 1,409,112 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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)
  • Exomes 𝑓: 7.1e-7 (0 hom.)
• Consequence: KDM4C NM_015061.6 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.74
• Publications: 6 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 -1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.44).
• BP7: Synonymous conserved (PhyloP=1.74 with no splicing effect.

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.618G>A	p.Glu206Glu	synonymous	Exon 5 of 22	NP_055876.2	Q9H3R0-1
	KDM4C	NM_001353997.3		c.618G>A	p.Glu206Glu	synonymous	Exon 5 of 23	NP_001340926.1
	KDM4C	NM_001304339.4		c.618G>A	p.Glu206Glu	synonymous	Exon 5 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.618G>A	p.Glu206Glu	synonymous	Exon 5 of 22	ENSP00000370710.3	Q9H3R0-1
	KDM4C	ENST00000536108.7	TSL:1	c.618G>A	p.Glu206Glu	synonymous	Exon 5 of 18	ENSP00000440656.4	Q9H3R0-3
	KDM4C	ENST00000948679.1		c.618G>A	p.Glu206Glu	synonymous	Exon 6 of 23	ENSP00000618738.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000419 AC: 1 AN: 238808 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000324

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: 7.10e-7 AC: 1 AN: 1409112 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 693666

African (AFR) AF: 0.00 AC: 0 AN: 32272

American (AMR) AF: 0.0000244 AC: 1 AN: 41014

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24866

East Asian (EAS) AF: 0.00 AC: 0 AN: 38596

South Asian (SAS) AF: 0.00 AC: 0 AN: 78448

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52248

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5564

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1078166

Other (OTH) AF: 0.00 AC: 0 AN: 57938

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.44
CADD	Benign	8.1
DANN	Benign	0.56
PhyloP100		1.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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: rs7864351; hg19: chr9-6849689;