Variant X-44873579-A-ACCGCCGCCGCTG details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP3BP6_Very_StrongBS1BS2

The NM_001291415.2(KDM6A):c.40_51dupGCCGCCGCCGCT(p.Ala14_Ala17dup) variant causes a conservative inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000241 in 1,197,292 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 104 hemizygotes in GnomAD. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.00016 ( 0 hom., 5 hem., cov: 23)

Exomes 𝑓: 0.00025 ( 0 hom. 99 hem. )

Consequence

KDM6A
NM_001291415.2 conservative_inframe_insertion

Scores

Not classified

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 0.977

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:

KDM6A (HGNC:):

KDM6A links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -17 ACMG points.

BP3

Nonframeshift variant in repetitive region in NM_001291415.2

BP6

Variant X-44873579-A-ACCGCCGCCGCTG is Benign according to our data. Variant chrX-44873579-A-ACCGCCGCCGCTG is described in ClinVar as [Likely_benign]. Clinvar id is 1164597.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.000159 (17/107232) while in subpopulation EAS AF= 0.000599 (2/3339). AF 95% confidence interval is 0.000149. There are 0 homozygotes in gnomad4. There are 5 alleles in male gnomad4 subpopulation. Median coverage is 23. This position pass quality control queck.

BS2

High Hemizygotes in GnomAd4 at 5 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KDM6A	NM_001291415.2 linkuse as main transcript	c.40_51dupGCCGCCGCCGCT	p.Ala14_Ala17dup	conservative_inframe_insertion	1/30	ENST00000611820.5	NP_001278344.1	A0A087X0R0B7ZKN5Q86TD1B7ZKN6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KDM6A	ENST00000611820.5 linkuse as main transcript	c.40_51dupGCCGCCGCCGCT	p.Ala14_Ala17dup	conservative_inframe_insertion	1/30	1	NM_001291415.2	ENSP00000483595.2		A0A087X0R0

Frequencies

GnomAD3 genomes

AF:

0.000159

AC:

AN:

107182

Hom.:

Cov.:

AF XY:

0.000160

AC XY:

AN XY:

31212

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000195

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000597

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000252

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000119

AC:

AN:

160255

Hom.:

AF XY:

0.000162

AC XY:

AN XY:

55573

show subpopulations

Gnomad AFR exome

AF:

0.000101

Gnomad AMR exome

AF:

0.0000765

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000233

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000250

AC:

272

AN:

1090060

Hom.:

Cov.:

AF XY:

0.000277

AC XY:

AN XY:

358010

show subpopulations

Gnomad4 AFR exome

AF:

0.0000761

Gnomad4 AMR exome

AF:

0.0000581

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000235

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000520

Gnomad4 NFE exome

AF:

0.000297

Gnomad4 OTH exome

AF:

0.000219

GnomAD4 genome

AF:

0.000159

AC:

AN:

107232

Hom.:

Cov.:

AF XY:

0.000160

AC XY:

AN XY:

31260

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000195

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000599

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000252

Gnomad4 OTH

AF:

0.00

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:4

Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Apr 01, 2023	KDM6A: BS2 -
Likely benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -
Likely benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -
Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 19, 2022	See Variant Classification Assertion Criteria. -

Kabuki syndrome 2

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 19, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

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