X-44873369-TGCCGCCGCCGCC-TGCCGCCGCCGCCGCCGCCGCCGCCGCC

Variant names:

• chrX-44873369-T-TGCCGCCGCCGCCGCC
• rs762577042
• NM_001291415.2:c.-179_-165dupGCCGCCGCCGCCGCC

Variant summary

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

The NM_001291415.2(KDM6A):​c.-179_-165dupGCCGCCGCCGCCGCC variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. It is difficult to determine the true allele frequency of this variant because it is of type INS_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: -0.304
• 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.-179_-165dupGCCGCCGCCGCCGCC		5_prime_UTR	Exon 1 of 30	NP_001278344.1	A0A087X0R0
	KDM6A	NM_001419809.1		c.-179_-165dupGCCGCCGCCGCCGCC		5_prime_UTR	Exon 1 of 31	NP_001406738.1
	KDM6A	NM_001419810.1		c.-179_-165dupGCCGCCGCCGCCGCC		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.-179_-165dupGCCGCCGCCGCCGCC		5_prime_UTR	Exon 1 of 30	ENSP00000483595.2	A0A087X0R0
	KDM6A	ENST00000382899.9	TSL:1	c.-179_-165dupGCCGCCGCCGCCGCC		5_prime_UTR	Exon 1 of 29	ENSP00000372355.6	F8W8R6
	KDM6A	ENST00000377967.9	TSL:1	c.-179_-165dupGCCGCCGCCGCCGCC		5_prime_UTR	Exon 1 of 29	ENSP00000367203.4	O15550

Frequencies

GnomAD3 genomes Cov.: 18

GnomAD4 exome AF: 0.00000217 AC: 1 AN: 460277 Hom.: 0 Cov.: 8 AF XY: 0.00 AC XY: 0 AN XY: 114251

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

American (AMR) AF: 0.00 AC: 0 AN: 11929

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: 0.000714 AC: 1 AN: 1400

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 333452

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

GnomAD4 genome Cov.: 18

Alfa AF: 0.00 Hom.: 99

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.30

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;