9-7076586-G-T

Variant names:

• chr9-7076586-G-T
• rs1570513
• ENST00000536108.7:c.*135G>T

Variant summary

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

The NM_001146696.2(KDM4C):​c.*135G>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000751 in 1,331,320 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: 7.5e-7 (0 hom.)
• Consequence: KDM4C NM_001146696.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.340
• Publications: 0 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=-0.91).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001146696.2. 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.2425-27099G>T		intron	N/A	NP_055876.2	Q9H3R0-1
	KDM4C	NM_001146696.2		c.*135G>T		3_prime_UTR	Exon 18 of 18	NP_001140168.1	Q9H3R0-4
	KDM4C	NM_001146695.4		c.*135G>T		3_prime_UTR	Exon 18 of 18	NP_001140167.1	Q9H3R0-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KDM4C	ENST00000536108.7	TSL:1	c.*135G>T		3_prime_UTR	Exon 18 of 18	ENSP00000440656.4	Q9H3R0-3
	KDM4C	ENST00000381309.8	TSL:1 MANE Select	c.2425-27099G>T		intron	N/A	ENSP00000370710.3	Q9H3R0-1
	KDM4C	ENST00000543771.5	TSL:2	c.*135G>T		3_prime_UTR	Exon 18 of 18	ENSP00000445427.1	Q9H3R0-3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.51e-7 AC: 1 AN: 1331320 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 652130

African (AFR) AF: 0.00 AC: 0 AN: 30156

American (AMR) AF: 0.00 AC: 0 AN: 30446

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22114

East Asian (EAS) AF: 0.00 AC: 0 AN: 34890

South Asian (SAS) AF: 0.00 AC: 0 AN: 68098

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 33850

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5408

European-Non Finnish (NFE) AF: 9.52e-7 AC: 1 AN: 1050914

Other (OTH) AF: 0.00 AC: 0 AN: 55444

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.23
DANN	Benign	0.46
PhyloP100		-0.34

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: rs1570513; hg19: chr9-7076586;