NM_015061.6:c.618G>C

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_015061.6(KDM4C):​c.618G>C​(p.Glu206Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000706 in 1,561,342 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0038 (2 hom., cov: 32)
  • Exomes 𝑓: 0.00037 (5 hom.)
• Consequence: KDM4C NM_015061.6 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• 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: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.010848165).
• BP6: Variant 9-6849689-G-C is Benign according to our data. Variant chr9-6849689-G-C is described in ClinVar as Benign. ClinVar VariationId is 714420.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd4 at 2 AR gene

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>C	p.Glu206Asp	missense	Exon 5 of 22	NP_055876.2	Q9H3R0-1
	KDM4C	NM_001353997.3		c.618G>C	p.Glu206Asp	missense	Exon 5 of 23	NP_001340926.1
	KDM4C	NM_001304339.4		c.618G>C	p.Glu206Asp	missense	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>C	p.Glu206Asp	missense	Exon 5 of 22	ENSP00000370710.3	Q9H3R0-1
	KDM4C	ENST00000536108.7	TSL:1	c.618G>C	p.Glu206Asp	missense	Exon 5 of 18	ENSP00000440656.4	Q9H3R0-3
	KDM4C	ENST00000948679.1		c.618G>C	p.Glu206Asp	missense	Exon 6 of 23	ENSP00000618738.1

Frequencies

GnomAD3 genomes AF: 0.00374 AC: 569 AN: 152116 Hom.: 2 Cov.: 32

Gnomad AFR AF: 0.0132

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000654

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000416

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00384

GnomAD2 exomes AF: 0.000963 AC: 230 AN: 238808 AF XY: 0.000659

Gnomad AFR exome AF: 0.0131

Gnomad AMR exome AF: 0.000454

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000273

Gnomad OTH exome AF: 0.000695

GnomAD4 exome AF: 0.000373 AC: 526 AN: 1409108 Hom.: 5 Cov.: 31 AF XY: 0.000301 AC XY: 209 AN XY: 693666

African (AFR) AF: 0.0132 AC: 426 AN: 32268

American (AMR) AF: 0.000658 AC: 27 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: 0.0000765 AC: 6 AN: 78448

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

Middle Eastern (MID) AF: 0.000539 AC: 3 AN: 5564

European-Non Finnish (NFE) AF: 0.0000102 AC: 11 AN: 1078166

Other (OTH) AF: 0.000915 AC: 53 AN: 57938

GnomAD4 genome AF: 0.00379 AC: 577 AN: 152234 Hom.: 2 Cov.: 32 AF XY: 0.00374 AC XY: 278 AN XY: 74424

African (AFR) AF: 0.0134 AC: 556 AN: 41542

American (AMR) AF: 0.000654 AC: 10 AN: 15300

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.000416 AC: 2 AN: 4808

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10608

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

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68010

Other (OTH) AF: 0.00380 AC: 8 AN: 2106

Alfa AF: 0.000291 Hom.: 0

Bravo AF: 0.00413

TwinsUK AF: 0.00 AC: 0

ALSPAC AF: 0.000259 AC: 1

ESP6500AA AF: 0.0102 AC: 45

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.00124 AC: 151

Asia WGS AF: 0.00202 AC: 7 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.87
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.14
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Benign	0.15	T
Eigen	Uncertain	0.22
Eigen_PC	Uncertain	0.27
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Uncertain	0.95	D
MetaRNN	Benign	0.011	T
MetaSVM	Benign	-0.49	T
MutationAssessor	Benign	1.9	L
PhyloP100		1.7
PrimateAI	Pathogenic	0.80	T
PROVEAN	Uncertain	-2.7	D
REVEL	Uncertain	0.33
Sift	Benign	0.040	D
Sift4G	Benign	0.15	T
Polyphen		0.65	P
Vest4		0.68
MutPred		0.27		Loss of ubiquitination at K208 (P = 0.1403)
MVP		0.61
MPC		0.21
ClinPred		0.017	T
GERP RS		3.9
Varity_R		0.76
gMVP		0.80
Mutation Taster		=94/6	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: rs7864351; hg19: chr9-6849689;