Variant rs5952285 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001291415.2(KDM6A):c.749-22T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0921 in 1,152,765 control chromosomes in the GnomAD database, including 9,819 homozygotes. There are 31,772 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 ( 4347 hom., 6876 hem., cov: 22)

Exomes 𝑓: 0.078 ( 5472 hom. 24896 hem. )

Consequence

KDM6A
NM_001291415.2 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 1.64

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 (BayesDel_noAF=-0.72).

BP6

Variant X-45053807-T-A is Benign according to our data. Variant chrX-45053807-T-A is described in ClinVar as [Benign]. Clinvar id is 1222327.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.601 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KDM6A	NM_001291415.2 linkuse as main transcript	c.749-22T>A		intron_variant		ENST00000611820.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KDM6A	ENST00000611820.5 linkuse as main transcript	c.749-22T>A		intron_variant		1	NM_001291415.2	P4

Frequencies

GnomAD3 genomes

AF:

0.219

AC:

24412

AN:

111426

Hom.:

4336

Cov.:

AF XY:

0.203

AC XY:

6845

AN XY:

33666

show subpopulations

Gnomad AFR

AF:

0.608

Gnomad AMI

AF:

0.0368

Gnomad AMR

AF:

0.112

Gnomad ASJ

AF:

0.0659

Gnomad EAS

AF:

0.0479

Gnomad SAS

AF:

0.137

Gnomad FIN

AF:

0.0313

Gnomad MID

AF:

0.143

Gnomad NFE

AF:

0.0659

Gnomad OTH

AF:

0.189

GnomAD3 exomes

AF:

0.106

AC:

19044

AN:

179523

Hom.:

2154

AF XY:

0.0938

AC XY:

6036

AN XY:

64361

show subpopulations

Gnomad AFR exome

AF:

0.615

Gnomad AMR exome

AF:

0.0600

Gnomad ASJ exome

AF:

0.0702

Gnomad EAS exome

AF:

0.0497

Gnomad SAS exome

AF:

0.135

Gnomad FIN exome

AF:

0.0328

Gnomad NFE exome

AF:

0.0620

Gnomad OTH exome

AF:

0.0847

GnomAD4 exome

AF:

0.0785

AC:

81716

AN:

1041288

Hom.:

5472

Cov.:

AF XY:

0.0777

AC XY:

24896

AN XY:

320434

show subpopulations

Gnomad4 AFR exome

AF:

0.625

Gnomad4 AMR exome

AF:

0.0661

Gnomad4 ASJ exome

AF:

0.0672

Gnomad4 EAS exome

AF:

0.0311

Gnomad4 SAS exome

AF:

0.131

Gnomad4 FIN exome

AF:

0.0326

Gnomad4 NFE exome

AF:

0.0611

Gnomad4 OTH exome

AF:

0.103

GnomAD4 genome

AF:

0.219

AC:

24461

AN:

111477

Hom.:

4347

Cov.:

AF XY:

0.204

AC XY:

6876

AN XY:

33727

show subpopulations

Gnomad4 AFR

AF:

0.609

Gnomad4 AMR

AF:

0.112

Gnomad4 ASJ

AF:

0.0659

Gnomad4 EAS

AF:

0.0472

Gnomad4 SAS

AF:

0.136

Gnomad4 FIN

AF:

0.0313

Gnomad4 NFE

AF:

0.0659

Gnomad4 OTH

AF:

0.189

Alfa

AF:

0.141

Hom.:

1323

Bravo

AF:

0.242

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

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

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.72

CADD

Benign

4.6

DANN

Benign

0.53

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

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