rs20539

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_001291415.2(KDM6A):c.3267G>A(p.Gln1089Gln) 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
NM_001291415.2 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: 1.88

Publications

26 publications found

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 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

KDM6A links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -19 ACMG points.

BP4

Computational evidence support a benign effect (REVEL=0.156).

BP6

Variant X-45079318-G-A is Benign according to our data. Variant chrX-45079318-G-A is described in ClinVar as Benign. ClinVar VariationId is 158689.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

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 rank	MANE	Protein	UniProt
KDM6A	NM_001291415.2 link	c.3267G>A	p.Gln1089Gln	synonymous_variant	Exon 21 of 30	ENST00000611820.5	NP_001278344.1	A0A087X0R0B7ZKN5Q86TD1B7ZKN6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KDM6A	ENST00000611820.5 link	c.3267G>A	p.Gln1089Gln	synonymous_variant	Exon 21 of 30	1	NM_001291415.2	ENSP00000483595.2		A0A087X0R0

Frequencies

GnomAD3 genomes

AF:

0.169

AC:

18636

AN:

110287

Hom.:

1626

Cov.:

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

GnomAD2 exomes

AF:

0.252

AC:

46012

AN:

182718

AF XY:

0.242

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 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

African (AFR)

AF:

0.0294

AC:

767

AN:

26124

American (AMR)

AF:

0.508

AC:

17838

AN:

35137

Ashkenazi Jewish (ASJ)

AF:

0.277

AC:

5336

AN:

19265

East Asian (EAS)

AF:

0.345

AC:

10388

AN:

30125

South Asian (SAS)

AF:

0.270

AC:

14471

AN:

53678

European-Finnish (FIN)

AF:

0.207

AC:

8404

AN:

40507

Middle Eastern (MID)

AF:

0.287

AC:

1175

AN:

4089

European-Non Finnish (NFE)

AF:

0.180

AC:

148521

AN:

824759

Other (OTH)

AF:

0.208

AC:

9459

AN:

45479

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.466

Heterozygous variant carriers

5191

10382

15572

20763

25954

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

5570

11140

16710

22280

27850

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.169

AC:

18620

AN:

110342

Hom.:

1620

Cov.:

AF XY:

0.170

AC XY:

5527

AN XY:

32606

show subpopulations

African (AFR)

AF:

0.0312

AC:

951

AN:

30497

American (AMR)

AF:

0.365

AC:

3758

AN:

10287

Ashkenazi Jewish (ASJ)

AF:

0.280

AC:

733

AN:

2618

East Asian (EAS)

AF:

0.324

AC:

1123

AN:

3469

South Asian (SAS)

AF:

0.281

AC:

730

AN:

2602

European-Finnish (FIN)

AF:

0.205

AC:

1176

AN:

5734

Middle Eastern (MID)

AF:

0.307

AC:

AN:

212

European-Non Finnish (NFE)

AF:

0.183

AC:

9662

AN:

52751

Other (OTH)

AF:

0.209

AC:

314

AN:

1500

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

511

1022

1532

2043

2554

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

200

400

600

800

1000

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.218

Hom.:

2827

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

Mar 22, 2016

Eurofins Ntd Llc (ga)

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Aug 01, 2013

Genetic Services Laboratory, University of Chicago

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Jan 24, 2024

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

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. -

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Jul 27, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Kabuki syndrome 2

Benign:2

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Aug 19, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.51

CADD

Benign

2.8

(source)

DANN

Benign

0.47

PhyloP100

1.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Mutation Taster

=99/1

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over