9-6793071-A-T

Variant names:

• chr9-6793071-A-T
• NM_015061.6:c.83A>T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_015061.6(KDM4C):​c.83A>T​(p.Glu28Val) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: KDM4C NM_015061.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.95

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

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KDM4C	NM_015061.6	c.83A>T	p.Glu28Val	missense_variant	Exon 2 of 22	ENST00000381309.8	NP_055876.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KDM4C	ENST00000381309.8	c.83A>T	p.Glu28Val	missense_variant	Exon 2 of 22	1	NM_015061.6	ENSP00000370710.3

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 31

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Dec 10, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.83A>T (p.E28V) alteration is located in exon 2 (coding exon 1) of the KDM4C gene. This alteration results from a A to T substitution at nucleotide position 83, causing the glutamic acid (E) at amino acid position 28 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.29
BayesDel_addAF	Benign	-0.032	T
BayesDel_noAF	Benign	-0.28
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Benign	0.13	.;.;.;T;.
Eigen	Benign	-0.043
Eigen_PC	Benign	0.15
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.95	D;D;D;D;D
M_CAP	Benign	0.011	T
MetaRNN	Uncertain	0.51	D;D;D;D;D
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.90	.;.;L;L;L
PrimateAI	Uncertain	0.50	T
PROVEAN	Pathogenic	-4.8	.;D;D;D;D
REVEL	Benign	0.26
Sift	Pathogenic	0.0	.;D;D;D;D
Sift4G	Pathogenic	0.0010	.;D;D;D;D
Polyphen		0.0090, 0.030, 0.015	.;B;B;B;.
Vest4		0.48, 0.53, 0.52, 0.51
MutPred		0.70		.;Loss of disorder (P = 0.0112);Loss of disorder (P = 0.0112);Loss of disorder (P = 0.0112);Loss of disorder (P = 0.0112);
MVP		0.28
MPC		0.082
ClinPred		0.98	D
GERP RS		5.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.81
gMVP		0.71

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr9-6793071;