X-45107550-T-C

Position:

• chrX-45107550-T-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001291415.2(KDM6A):​c.4161+14T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.092 in 1,205,888 control chromosomes in the GnomAD database, including 9,868 homozygotes. There are 35,243 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.22 (4281 hom., 6721 hem., cov: 22)
  • Exomes 𝑓: 0.079 (5587 hom. 28522 hem.)
• Consequence: KDM6A NM_001291415.2 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:7
• Conservation: PhyloP100: -0.0720

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant X-45107550-T-C is Benign according to our data. Variant chrX-45107550-T-C is described in ClinVar as [Benign]. Clinvar id is 158690.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.596 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KDM6A	NM_001291415.2	c.4161+14T>C		intron_variant		ENST00000611820.5	NP_001278344.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KDM6A	ENST00000611820.5	c.4161+14T>C		intron_variant		1	NM_001291415.2	ENSP00000483595.2

Frequencies

GnomAD3 genomes AF: 0.217 AC: 24131 AN: 111264 Hom.: 4270 Cov.: 22 AF XY: 0.200 AC XY: 6690 AN XY: 33520

Gnomad AFR AF: 0.603

Gnomad AMI AF: 0.0336

Gnomad AMR AF: 0.111

Gnomad ASJ AF: 0.0661

Gnomad EAS AF: 0.0493

Gnomad SAS AF: 0.141

Gnomad FIN AF: 0.0300

Gnomad MID AF: 0.136

Gnomad NFE AF: 0.0651

Gnomad OTH AF: 0.186

GnomAD3 exomes AF: 0.106 AC: 19484 AN: 183025 Hom.: 2142 AF XY: 0.0959 AC XY: 6476 AN XY: 67559

Gnomad AFR exome AF: 0.611

Gnomad AMR exome AF: 0.0597

Gnomad ASJ exome AF: 0.0701

Gnomad EAS exome AF: 0.0504

Gnomad SAS exome AF: 0.135

Gnomad FIN exome AF: 0.0331

Gnomad NFE exome AF: 0.0625

Gnomad OTH exome AF: 0.0851

GnomAD4 exome AF: 0.0793 AC: 86791 AN: 1094571 Hom.: 5587 Cov.: 28 AF XY: 0.0791 AC XY: 28522 AN XY: 360617

Gnomad4 AFR exome AF: 0.623

Gnomad4 AMR exome AF: 0.0658

Gnomad4 ASJ exome AF: 0.0679

Gnomad4 EAS exome AF: 0.0317

Gnomad4 SAS exome AF: 0.132

Gnomad4 FIN exome AF: 0.0327

Gnomad4 NFE exome AF: 0.0621

Gnomad4 OTH exome AF: 0.103

GnomAD4 genome AF: 0.217 AC: 24180 AN: 111317 Hom.: 4281 Cov.: 22 AF XY: 0.200 AC XY: 6721 AN XY: 33583

Gnomad4 AFR AF: 0.603

Gnomad4 AMR AF: 0.111

Gnomad4 ASJ AF: 0.0661

Gnomad4 EAS AF: 0.0487

Gnomad4 SAS AF: 0.141

Gnomad4 FIN AF: 0.0300

Gnomad4 NFE AF: 0.0652

Gnomad4 OTH AF: 0.186

Alfa AF: 0.148 Hom.: 1660

Bravo AF: 0.240

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:3

Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Oct 20, 2015	- -
Benign, criteria provided, single submitter	clinical testing	Genetic Services Laboratory, University of Chicago	Sep 10, 2013	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 03, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Kabuki syndrome 2 Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Aug 19, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	2.5
DANN	Benign	0.64

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

Publications

LitVar

Other links and lift over

dbSNP: rs5952682; hg19: chrX-44966795; COSMIC: COSV65037578;