9-7165427-G-C

Variant names:

• chr9-7165427-G-C
• rs10976082
• NM_015061.6:c.2901+70G>C

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.2901+70G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000799 in 1,376,872 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: 33)
  • Exomes 𝑓: 0.0000080 (0 hom.)
• Consequence: KDM4C NM_015061.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0710
• Publications: 2 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 (BayesDel_noAF=-0.83).

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KDM4C	NM_015061.6	MANE Select	c.2901+70G>C		intron	N/A	NP_055876.2
	KDM4C	NM_001353997.3		c.3000+70G>C		intron	N/A	NP_001340926.1
	KDM4C	NM_001304339.4		c.2901+70G>C		intron	N/A	NP_001291268.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KDM4C	ENST00000381309.8	TSL:1 MANE Select	c.2901+70G>C		intron	N/A	ENSP00000370710.3
	KDM4C	ENST00000381306.7	TSL:2	c.2901+70G>C		intron	N/A	ENSP00000370707.3
	KDM4C	ENST00000428870.6	TSL:2	c.1962+70G>C		intron	N/A	ENSP00000405739.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000799 AC: 11 AN: 1376872 Hom.: 0 AF XY: 0.00000732 AC XY: 5 AN XY: 683214

African (AFR) AF: 0.00 AC: 0 AN: 31132

American (AMR) AF: 0.00 AC: 0 AN: 38738

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23096

East Asian (EAS) AF: 0.000155 AC: 6 AN: 38650

South Asian (SAS) AF: 0.00 AC: 0 AN: 77170

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51076

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5136

European-Non Finnish (NFE) AF: 0.00000474 AC: 5 AN: 1054740

Other (OTH) AF: 0.00 AC: 0 AN: 57134

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 7

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	1.0
DANN	Benign	0.69
PhyloP100		0.071
Mutation Taster		=100/0	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: rs10976082; hg19: chr9-7165427;