rs10605935

Variant names:

• chrX-45076679-CTTTT-C
• rs10605935
• NM_001291415.2:c.2859-8_2859-5delTTTT

Your query was ambiguous. Multiple possible variants found:

• chrX-45076679-CTTTT-C
• chrX-45076679-CTTTT-CT
• chrX-45076679-CTTTT-CTT
• chrX-45076679-CTTTT-CTTT
• chrX-45076679-CTTTT-CTTTTT
• chrX-45076679-CTTTT-CTTTTTT

Variant summary

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

The NM_001291415.2(KDM6A):​c.2859-8_2859-5delTTTT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000177 in 734,786 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. There is a variant allele frequency bias in the population database for this variant (GnomAdExome4), which may indicate mosaicism or somatic mutations in the reference population data. 1/1 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 0)
  • Exomes 𝑓: 0.000018 (0 hom. 0 hem.)
• Consequence: KDM6A NM_001291415.2 splice_region, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.198
• Publications: 5 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: ClinGen, Ambry Genetics, Labcorp Genetics (formerly Invitae), G2P
• 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KDM6A	NM_001291415.2	MANE Select	c.2859-8_2859-5delTTTT		splice_region intron	N/A	NP_001278344.1
	KDM6A	NM_001419809.1		c.2859-8_2859-5delTTTT		splice_region intron	N/A	NP_001406738.1
	KDM6A	NM_001419810.1		c.2757-8_2757-5delTTTT		splice_region intron	N/A	NP_001406739.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KDM6A	ENST00000611820.5	TSL:1 MANE Select	c.2859-8_2859-5delTTTT		splice_region intron	N/A	ENSP00000483595.2
	KDM6A	ENST00000382899.9	TSL:1	c.2724-8_2724-5delTTTT		splice_region intron	N/A	ENSP00000372355.6
	KDM6A	ENST00000377967.9	TSL:1	c.2703-8_2703-5delTTTT		splice_region intron	N/A	ENSP00000367203.4

Frequencies

GnomAD3 genomes Cov.: 0

GnomAD2 exomes AF: 0.00 AC: 0 AN: 79362 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000177 AC: 13 AN: 734786 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 211450

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 19684

American (AMR) AF: 0.00 AC: 0 AN: 25758

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 14097

East Asian (EAS) AF: 0.00 AC: 0 AN: 24683

South Asian (SAS) AF: 0.00 AC: 0 AN: 39262

European-Finnish (FIN) AF: 0.0000306 AC: 1 AN: 32659

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3028

European-Non Finnish (NFE) AF: 0.0000221 AC: 12 AN: 543474

Other (OTH) AF: 0.00 AC: 0 AN: 32141

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.20

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		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: rs10605935; hg19: chrX-44935924;