NM_018039.3:c.947G>A

Variant names:

• chr11-94998319-G-A
• rs782044085
• NM_018039.3:c.947G>A

Variant summary

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

The NM_018039.3(KDM4D):​c.947G>A​(p.Arg316Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R316T) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: KDM4D NM_018039.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.83
• Publications: 0 publications found

Genes affected

KDM4D (HGNC:25498): (lysine demethylase 4D) Enables histone H3-methyl-lysine-9 demethylase activity. Involved in histone H3-K9 demethylation. Acts upstream of or within several processes, including cellular response to ionizing radiation; positive regulation of chromatin binding activity; and positive regulation of double-strand break repair via nonhomologous end joining. Located in site of double-strand break. Biomarker of nephroblastoma. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000299693 (HGNC:):

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 (MetaRNN=0.058801502).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018039.3. 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
	KDM4D	NM_018039.3	MANE Select	c.947G>A	p.Arg316Lys	missense	Exon 3 of 3	NP_060509.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KDM4D	ENST00000335080.6	TSL:1 MANE Select	c.947G>A	p.Arg316Lys	missense	Exon 3 of 3	ENSP00000334181.5	Q6B0I6
	KDM4D	ENST00000536741.1	TSL:4	c.947G>A	p.Arg316Lys	missense	Exon 2 of 2	ENSP00000460897.1	Q6B0I6
	KDM4D	ENST00000610872.1	TSL:6	c.947G>A	p.Arg316Lys	missense	Exon 1 of 1	ENSP00000482224.1	Q6B0I6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.52
CADD	Benign	23
DANN	Benign	0.96
DEOGEN2	Benign	0.051	T
Eigen	Benign	-0.54
Eigen_PC	Benign	-0.49
FATHMM_MKL	Uncertain	0.87	D
LIST_S2	Benign	0.19	T
M_CAP	Benign	0.0055	T
MetaRNN	Benign	0.059	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.6	L
PhyloP100		2.8
PrimateAI	Benign	0.41	T
PROVEAN	Benign	-1.4	N
REVEL	Benign	0.056
Sift	Benign	0.98	T
Sift4G	Benign	0.48	T
Polyphen		0.020	B
Vest4		0.16
MutPred		0.49		Gain of ubiquitination at R316 (P = 0.0238)
MVP		0.21
MPC		0.61
ClinPred		0.36	T
GERP RS		1.8
Varity_R		0.43
gMVP		0.74
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: rs782044085; hg19: chr11-94731483;