Genetic Variant KDM6A:c.2859-6_2859-5delTT (chrX-45076679-CTT-C) – ACMG Classification: Benign (-16 pts)

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1

The NM_001291415.2(KDM6A):c.2859-6_2859-5delTT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.223 in 685,890 control chromosomes in the GnomAD database, including 3,708 homozygotes. There are 20,772 hemizygotes in GnomAD. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.12 ( 635 hom., 2188 hem., cov: 0)

Exomes 𝑓: 0.24 ( 3073 hom. 18584 hem. )

Consequence

KDM6A
NM_001291415.2 splice_region, intron

Scores

Not classified

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.198

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP6

Variant X-45076679-CTT-C is Benign according to our data. Variant chrX-45076679-CTT-C is described in ClinVar as [Likely_benign]. Clinvar id is 167213.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chrX-45076679-CTT-C is described in Lovd as [Likely_benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.36 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KDM6A	NM_001291415.2 link	c.2859-6_2859-5delTT		splice_region_variant, intron_variant	Intron 18 of 29	ENST00000611820.5	NP_001278344.1	A0A087X0R0B7ZKN5Q86TD1B7ZKN6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KDM6A	ENST00000611820.5 link	c.2859-6_2859-5delTT		splice_region_variant, intron_variant	Intron 18 of 29	1	NM_001291415.2	ENSP00000483595.2		A0A087X0R0

Frequencies

GnomAD3 genomes

AF:

0.123

AC:

10866

AN:

88221

Hom.:

635

Cov.:

AF XY:

0.131

AC XY:

2189

AN XY:

16707

show subpopulations

Gnomad AFR

AF:

0.0761

Gnomad AMI

AF:

0.0403

Gnomad AMR

AF:

0.0686

Gnomad ASJ

AF:

0.146

Gnomad EAS

AF:

0.378

Gnomad SAS

AF:

0.265

Gnomad FIN

AF:

0.183

Gnomad MID

AF:

0.104

Gnomad NFE

AF:

0.133

Gnomad OTH

AF:

0.122

GnomAD3 exomes

AF:

0.329

AC:

26110

AN:

79362

Hom.:

321

AF XY:

0.331

AC XY:

2313

AN XY:

6988

show subpopulations

Gnomad AFR exome

AF:

0.161

Gnomad AMR exome

AF:

0.271

Gnomad ASJ exome

AF:

0.343

Gnomad EAS exome

AF:

0.435

Gnomad SAS exome

AF:

0.408

Gnomad FIN exome

AF:

0.360

Gnomad NFE exome

AF:

0.344

Gnomad OTH exome

AF:

0.312

GnomAD4 exome

AF:

0.237

AC:

141928

AN:

597667

Hom.:

3073

AF XY:

0.140

AC XY:

18584

AN XY:

132807

show subpopulations

Gnomad4 AFR exome

AF:

0.117

Gnomad4 AMR exome

AF:

0.219

Gnomad4 ASJ exome

AF:

0.264

Gnomad4 EAS exome

AF:

0.440

Gnomad4 SAS exome

AF:

0.281

Gnomad4 FIN exome

AF:

0.306

Gnomad4 NFE exome

AF:

0.227

Gnomad4 OTH exome

AF:

0.240

GnomAD4 genome

AF:

0.123

AC:

10866

AN:

88223

Hom.:

635

Cov.:

AF XY:

0.131

AC XY:

2188

AN XY:

16727

show subpopulations

Gnomad4 AFR

AF:

0.0762

Gnomad4 AMR

AF:

0.0685

Gnomad4 ASJ

AF:

0.146

Gnomad4 EAS

AF:

0.378

Gnomad4 SAS

AF:

0.266

Gnomad4 FIN

AF:

0.183

Gnomad4 NFE

AF:

0.133

Gnomad4 OTH

AF:

0.128

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Oct 15, 2014

Eurofins Ntd Llc (ga)

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided

Benign:1

Aug 13, 2019

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Kabuki syndrome 2

Benign:1

Jan 23, 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

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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.

X-45076679-CTTTT-CTT

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