rs34922269

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_001291415.2(KDM6A):c.1897A>G(p.Thr633Ala) variant causes a missense change. The variant allele was found at a frequency of 0.00114 in 1,208,652 control chromosomes in the GnomAD database, including 9 homozygotes. There are 363 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0058 ( 5 hom., 166 hem., cov: 22)

Exomes 𝑓: 0.00066 ( 4 hom. 197 hem. )

Consequence

KDM6A
NM_001291415.2 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 6.71

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.007016927).

BP6

Variant X-45063635-A-G is Benign according to our data. Variant chrX-45063635-A-G is described in ClinVar as [Benign]. Clinvar id is 261405.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chrX-45063635-A-G is described in Lovd as [Likely_benign].

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00585 (653/111626) while in subpopulation AFR AF= 0.02 (615/30687). AF 95% confidence interval is 0.0187. There are 5 homozygotes in gnomad4. There are 166 alleles in male gnomad4 subpopulation. Median coverage is 22. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 5 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KDM6A	NM_001291415.2 link	c.1897A>G	p.Thr633Ala	missense_variant	Exon 17 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.1897A>G	p.Thr633Ala	missense_variant	Exon 17 of 30	1	NM_001291415.2	ENSP00000483595.2		A0A087X0R0

Frequencies

GnomAD3 genomes

AF:

0.00583

AC:

650

AN:

111574

Hom.:

Cov.:

AF XY:

0.00489

AC XY:

165

AN XY:

33758

show subpopulations

Gnomad AFR

AF:

0.0200

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00247

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000371

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000151

Gnomad OTH

AF:

0.00266

GnomAD3 exomes

AF:

0.00175

AC:

317

AN:

181660

Hom.:

AF XY:

0.00110

AC XY:

AN XY:

66246

show subpopulations

Gnomad AFR exome

AF:

0.0213

Gnomad AMR exome

AF:

0.00106

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000530

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000989

Gnomad OTH exome

AF:

0.000223

GnomAD4 exome

AF:

0.000657

AC:

721

AN:

1097026

Hom.:

Cov.:

AF XY:

0.000544

AC XY:

197

AN XY:

362408

show subpopulations

Gnomad4 AFR exome

AF:

0.0213

Gnomad4 AMR exome

AF:

0.00134

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000740

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000499

Gnomad4 OTH exome

AF:

0.00141

GnomAD4 genome

AF:

0.00585

AC:

653

AN:

111626

Hom.:

Cov.:

AF XY:

0.00491

AC XY:

166

AN XY:

33820

show subpopulations

Gnomad4 AFR

AF:

0.0200

Gnomad4 AMR

AF:

0.00247

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000151

Gnomad4 OTH

AF:

0.00263

Alfa

AF:

0.00107

Hom.:

Bravo

AF:

0.00677

ESP6500AA

AF:

0.0167

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.00193

AC:

234

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Dec 27, 2018

Genetic Services Laboratory, University of Chicago

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Sep 25, 2020

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Kabuki syndrome 2

Benign:1

Jan 27, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.071

BayesDel_addAF

Benign

-0.47

BayesDel_noAF

Benign

-0.42

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.025

.;T;.;T;T

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.93

D;D;D;D;D

MetaRNN

Benign

0.0070

T;T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.81

.;.;.;.;L

PrimateAI

Uncertain

0.51

PROVEAN

Benign

-2.2

.;.;.;.;N

REVEL

Benign

0.21

Sift

Uncertain

0.013

.;.;.;.;D

Sift4G

Benign

0.74

T;T;T;T;T

Polyphen

0.82

.;.;.;.;P

Vest4

0.46

MVP

0.48

MPC

0.11

ClinPred

0.052

GERP RS

5.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.48

gMVP

0.43

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