rs1556308480

Positions:

• chrX-45059287-C-A
• chrX-45059287-C-G
• chrX-45059287-C-T

Variant summary

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

The NM_001291415.2(KDM6A):​c.1015C>A​(p.Gln339Lys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 22)
• Consequence: KDM6A NM_001291415.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.57

Genes affected

KDM6A (HGNC:12637): (lysine demethylase 6A) This gene is located on the X chromosome and is the corresponding locus to a Y-linked gene which encodes a tetratricopeptide repeat (TPR) protein. The encoded protein of this gene contains a JmjC-domain and catalyzes the demethylation of tri/dimethylated histone H3. Multiple alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Apr 2014]

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	UniProt
KDM6A	NM_001291415.2	c.1015C>A	p.Gln339Lys	missense_variant	12/30	ENST00000611820.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KDM6A	ENST00000611820.5	c.1015C>A	p.Gln339Lys	missense_variant	12/30	1	NM_001291415.2	P4

Frequencies

GnomAD3 genomes Cov.: 22

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 22

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.99
BayesDel_addAF	Pathogenic	0.16	D
BayesDel_noAF	Uncertain	0.0
CADD	Uncertain	24
DANN	Uncertain	0.99
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.97	D;D;D;D;D
M_CAP	Uncertain	0.11	D
MetaRNN	Uncertain	0.49	T;T;T;T;T
MetaSVM	Benign	-0.68	T
MutationTaster	Benign	1.0	D;D;D;D
PrimateAI	Pathogenic	0.89	D
Sift4G	Uncertain	0.0020	D;D;D;D;D
Polyphen		1.0	.;.;.;.;D
Vest4		0.66
MutPred		0.47		.;.;.;.;Gain of ubiquitination at Q339 (P = 0.0267);
MVP		0.73
MPC		2.0
ClinPred		0.98	D
GERP RS		5.6
Varity_R		0.93
gMVP		0.72

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: chrX-44918532;