rs20539

Positions:

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The ENST00000611820.5(KDM6A):c.3267G>A(p.Gln1089=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.198 in 1,189,505 control chromosomes in the GnomAD database, including 18,401 homozygotes. There are 76,408 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.17 ( 1620 hom., 5527 hem., cov: 22)

Exomes 𝑓: 0.20 ( 16781 hom. 70881 hem. )

Consequence

KDM6A
ENST00000611820.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:10

Conservation

PhyloP100: 1.88

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.51).

BP6

Variant X-45079318-G-A is Benign according to our data. Variant chrX-45079318-G-A is described in ClinVar as [Benign]. Clinvar id is 158689.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chrX-45079318-G-A is described in Lovd as [Likely_benign]. Variant chrX-45079318-G-A is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=1.88 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.356 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KDM6A	NM_001291415.2 linkuse as main transcript	c.3267G>A	p.Gln1089=	synonymous_variant	21/30	ENST00000611820.5	NP_001278344.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KDM6A	ENST00000611820.5 linkuse as main transcript	c.3267G>A	p.Gln1089=	synonymous_variant	21/30	1	NM_001291415.2	ENSP00000483595	P4

Frequencies

GnomAD3 genomes

AF:

0.169

AC:

18636

AN:

110287

Hom.:

1626

Cov.:

AF XY:

0.170

AC XY:

5522

AN XY:

32543

show subpopulations

Gnomad AFR

AF:

0.0313

Gnomad AMI

AF:

0.161

Gnomad AMR

AF:

0.366

Gnomad ASJ

AF:

0.280

Gnomad EAS

AF:

0.323

Gnomad SAS

AF:

0.281

Gnomad FIN

AF:

0.205

Gnomad MID

AF:

0.307

Gnomad NFE

AF:

0.183

Gnomad OTH

AF:

0.211

GnomAD3 exomes

AF:

0.252

AC:

46012

AN:

182718

Hom.:

5160

AF XY:

0.242

AC XY:

16291

AN XY:

67236

show subpopulations

Gnomad AFR exome

AF:

0.0287

Gnomad AMR exome

AF:

0.529

Gnomad ASJ exome

AF:

0.275

Gnomad EAS exome

AF:

0.325

Gnomad SAS exome

AF:

0.270

Gnomad FIN exome

AF:

0.203

Gnomad NFE exome

AF:

0.186

Gnomad OTH exome

AF:

0.255

GnomAD4 exome

AF:

0.200

AC:

216359

AN:

1079163

Hom.:

16781

Cov.:

AF XY:

0.204

AC XY:

70881

AN XY:

347453

show subpopulations

Gnomad4 AFR exome

AF:

0.0294

Gnomad4 AMR exome

AF:

0.508

Gnomad4 ASJ exome

AF:

0.277

Gnomad4 EAS exome

AF:

0.345

Gnomad4 SAS exome

AF:

0.270

Gnomad4 FIN exome

AF:

0.207

Gnomad4 NFE exome

AF:

0.180

Gnomad4 OTH exome

AF:

0.208

GnomAD4 genome

AF:

0.169

AC:

18620

AN:

110342

Hom.:

1620

Cov.:

AF XY:

0.170

AC XY:

5527

AN XY:

32606

show subpopulations

Gnomad4 AFR

AF:

0.0312

Gnomad4 AMR

AF:

0.365

Gnomad4 ASJ

AF:

0.280

Gnomad4 EAS

AF:

0.324

Gnomad4 SAS

AF:

0.281

Gnomad4 FIN

AF:

0.205

Gnomad4 NFE

AF:

0.183

Gnomad4 OTH

AF:

0.209

Alfa

AF:

0.224

Hom.:

2697

Bravo

AF:

0.182

ClinVar

Significance: Benign

Submissions summary: Benign:10

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:6

Benign, criteria provided, single submitter	clinical testing	Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan	Jan 24, 2024	This variant is classified as Benign based on local population frequency. This variant was detected in 45% of patients studied by a panel of primary immunodeficiencies. Number of patients: 43. Only high quality variants are reported. -
Benign, criteria provided, single submitter	clinical testing	Genetic Services Laboratory, University of Chicago	Aug 01, 2013	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Mar 22, 2016	- -
Benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -
Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 27, 2018	- -

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

-0.51

CADD

Benign

2.8

DANN

Benign

0.47

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over