chrX-44873369-TGCCGCCGCCGCC-T

Variant names:

• chrX-44873369-TGCCGCCGCCGCC-T
• rs762577042
• NM_001291415.2:c.-176_-165delGCCGCCGCCGCC

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_001291415.2(KDM6A):​c.-176_-165delGCCGCCGCCGCC variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000217 in 460,280 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. It is difficult to determine the true allele frequency of this variant because it is of type DEL_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 18)
  • Exomes 𝑓: 0.0000022 (0 hom. 0 hem.)
• Consequence: KDM6A NM_001291415.2 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.21
• 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: Uncertain_significance. The variant received 0 ACMG points.

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.-176_-165delGCCGCCGCCGCC		5_prime_UTR	Exon 1 of 30	NP_001278344.1	A0A087X0R0
	KDM6A	NM_001419809.1		c.-176_-165delGCCGCCGCCGCC		5_prime_UTR	Exon 1 of 31	NP_001406738.1
	KDM6A	NM_001419810.1		c.-176_-165delGCCGCCGCCGCC		5_prime_UTR	Exon 1 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.-176_-165delGCCGCCGCCGCC		5_prime_UTR	Exon 1 of 30	ENSP00000483595.2	A0A087X0R0
	KDM6A	ENST00000382899.9	TSL:1	c.-176_-165delGCCGCCGCCGCC		5_prime_UTR	Exon 1 of 29	ENSP00000372355.6	F8W8R6
	KDM6A	ENST00000377967.9	TSL:1	c.-176_-165delGCCGCCGCCGCC		5_prime_UTR	Exon 1 of 29	ENSP00000367203.4	O15550

Frequencies

GnomAD3 genomes Cov.: 18

GnomAD4 exome AF: 0.00000217 AC: 1 AN: 460280 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 114252

African (AFR) AF: 0.00 AC: 0 AN: 8791

American (AMR) AF: 0.00 AC: 0 AN: 11930

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 8836

East Asian (EAS) AF: 0.00 AC: 0 AN: 18251

South Asian (SAS) AF: 0.00 AC: 0 AN: 29090

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 26775

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1400

European-Non Finnish (NFE) AF: 0.00000300 AC: 1 AN: 333454

Other (OTH) AF: 0.00 AC: 0 AN: 21753

GnomAD4 genome Cov.: 18

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.2

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs762577042; hg19: chrX-44732615;