rs17215160

Variant names:

• chrX-45018134-A-T
• rs17215160
• NM_001291415.2:c.444-2476A>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001291415.2(KDM6A):​c.444-2476A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0747 in 111,120 control chromosomes in the GnomAD database, including 310 homozygotes. There are 2,312 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.075 (310 hom., 2312 hem., cov: 23)
• Consequence: KDM6A NM_001291415.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.400
• 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: ClinGen, Ambry Genetics, Labcorp Genetics (formerly Invitae), G2P
• Kabuki syndrome

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.109 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KDM6A	NM_001291415.2	c.444-2476A>T		intron_variant	Intron 5 of 29	ENST00000611820.5	NP_001278344.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KDM6A	ENST00000611820.5	c.444-2476A>T		intron_variant	Intron 5 of 29	1	NM_001291415.2	ENSP00000483595.2

Frequencies

GnomAD3 genomes AF: 0.0747 AC: 8300 AN: 111064 Hom.: 310 Cov.: 23

Gnomad AFR AF: 0.0166

Gnomad AMI AF: 0.140

Gnomad AMR AF: 0.0621

Gnomad ASJ AF: 0.108

Gnomad EAS AF: 0.00140

Gnomad SAS AF: 0.0287

Gnomad FIN AF: 0.114

Gnomad MID AF: 0.0336

Gnomad NFE AF: 0.111

Gnomad OTH AF: 0.0783

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0747 AC: 8296 AN: 111120 Hom.: 310 Cov.: 23 AF XY: 0.0694 AC XY: 2312 AN XY: 33314

African (AFR) AF: 0.0165 AC: 506 AN: 30629

American (AMR) AF: 0.0618 AC: 644 AN: 10420

Ashkenazi Jewish (ASJ) AF: 0.108 AC: 286 AN: 2637

East Asian (EAS) AF: 0.00141 AC: 5 AN: 3552

South Asian (SAS) AF: 0.0295 AC: 79 AN: 2675

European-Finnish (FIN) AF: 0.114 AC: 673 AN: 5918

Middle Eastern (MID) AF: 0.0369 AC: 8 AN: 217

European-Non Finnish (NFE) AF: 0.111 AC: 5883 AN: 52874

Other (OTH) AF: 0.0766 AC: 116 AN: 1514

Alfa AF: 0.0855 Hom.: 489

Bravo AF: 0.0698

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.19
DANN	Benign	0.69
PhyloP100		-0.40
Mutation Taster		=100/0	polymorphism (auto)

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: rs17215160; hg19: chrX-44877379;