X-45069887-C-G

Variant names:

• chrX-45069887-C-G
• rs35467614
• NM_001291415.2:c.2388C>G

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 2P and 3B. PM2 BP4_Moderate BP7

The NM_001291415.2(KDM6A):​c.2388C>G​(p.Val796Val) variant causes a synonymous 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. V796V) has been classified as Benign.

• Frequency: Genomes: not found (cov: 23)
• Consequence: KDM6A NM_001291415.2 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0230
• Publications: 0 publications found

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]

KDM6A Gene-Disease associations (from GenCC):

• Kabuki syndrome 2

  Inheritance: XL Classification: DEFINITIVE, STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics, ClinGen
• Kabuki syndrome

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Likely_benign. The variant received -1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (REVEL=0.047).
• BP7: Synonymous conserved (PhyloP=0.023 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001291415.2. 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
	KDM6A	NM_001291415.2	MANE Select	c.2388C>G	p.Val796Val	synonymous	Exon 18 of 30	NP_001278344.1	A0A087X0R0
	KDM6A	NM_001419809.1		c.2388C>G	p.Val796Val	synonymous	Exon 18 of 31	NP_001406738.1
	KDM6A	NM_001419810.1		c.2286C>G	p.Val762Val	synonymous	Exon 17 of 30	NP_001406739.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KDM6A	ENST00000611820.5	TSL:1 MANE Select	c.2388C>G	p.Val796Val	synonymous	Exon 18 of 30	ENSP00000483595.2	A0A087X0R0
	KDM6A	ENST00000382899.9	TSL:1	c.2253C>G	p.Val751Val	synonymous	Exon 17 of 29	ENSP00000372355.6	F8W8R6
	KDM6A	ENST00000377967.9	TSL:1	c.2232C>G	p.Val744Val	synonymous	Exon 17 of 29	ENSP00000367203.4	O15550

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 23

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.56
CADD	Benign	1.0
DANN	Benign	0.69
PhyloP100		0.023

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: rs35467614; hg19: chrX-44929132;