chr1-43703667-A-T

Position:

• chr1-43703667-A-T

Variant summary

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

The NM_014663.3(KDM4A):​c.2892A>T​(p.Gln964His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: KDM4A NM_014663.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.03

Genes affected

KDM4A (HGNC:22978): (lysine demethylase 4A) This gene is a member of the Jumonji domain 2 (JMJD2) family and encodes a protein containing a JmjN domain, a JmjC domain, a JD2H domain, two TUDOR domains, and two PHD-type zinc fingers. This nuclear protein functions as a trimethylation-specific demethylase, converting specific trimethylated histone residues to the dimethylated form, and as a transcriptional repressor. [provided by RefSeq, Apr 2009]

ENSG00000284989 (HGNC:):

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/exons	MANE	Protein	UniProt
KDM4A	NM_014663.3	c.2892A>T	p.Gln964His	missense_variant	20/22	ENST00000372396.4	NP_055478.2
KDM4A-AS1	NR_033827.1	n.389-20T>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KDM4A	ENST00000372396.4	c.2892A>T	p.Gln964His	missense_variant	20/22	1	NM_014663.3	ENSP00000361473.3
ENSG00000284989	ENST00000645057.1	n.*1130A>T		non_coding_transcript_exon_variant	14/26			ENSP00000494063.1
ENSG00000284989	ENST00000645057.1	n.*1130A>T		3_prime_UTR_variant	14/26			ENSP00000494063.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 05, 2024

The c.2892A>T (p.Q964H) alteration is located in exon 20 (coding exon 19) of the KDM4A gene. This alteration results from a A to T substitution at nucleotide position 2892, causing the glutamine (Q) at amino acid position 964 to be replaced by a histidine (H). 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	Pathogenic	0.63
BayesDel_addAF	Uncertain	0.023	T
BayesDel_noAF	Benign	-0.21
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.18	T
Eigen	Uncertain	0.42
Eigen_PC	Uncertain	0.43
FATHMM_MKL	Uncertain	0.86	D
LIST_S2	Uncertain	0.95	D
M_CAP	Benign	0.022	T
MetaRNN	Uncertain	0.49	T
MetaSVM	Benign	-0.88	T
MutationAssessor	Uncertain	2.3	M
PrimateAI	Uncertain	0.74	T
PROVEAN	Uncertain	-2.9	D
REVEL	Benign	0.18
Sift	Benign	0.077	T
Sift4G	Benign	0.25	T
Polyphen		1.0	D
Vest4		0.63
MutPred		0.27		Loss of helix (P = 0.0376);
MVP		0.35
MPC		1.3
ClinPred		0.89	D
GERP RS		5.0
Varity_R		0.62
gMVP		0.59

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: chr1-44169338;