Variant X-44873590-T-TGCC 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.48_50dup(p.Ala16dup) variant causes a inframe insertion change. The variant allele was found at a frequency of 0.00113 in 1,203,989 control chromosomes in the GnomAD database, including 9 homozygotes. There are 352 hemizygotes in GnomAD. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0058 ( 5 hom., 161 hem., cov: 23)

Exomes 𝑓: 0.00066 ( 4 hom. 191 hem. )

Consequence

KDM6A
NM_001291415.2 inframe_insertion

Scores

Not classified

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 4.02

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 -17 ACMG points.

BP3

Nonframeshift variant in repetitive region in NM_001291415.2

BP6

Variant X-44873590-T-TGCC is Benign according to our data. Variant chrX-44873590-T-TGCC is described in ClinVar as [Likely_benign]. Clinvar id is 193446.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0058 (642/110759) while in subpopulation AFR AF= 0.0199 (605/30456). AF 95% confidence interval is 0.0186. There are 5 homozygotes in gnomad4. There are 161 alleles in male gnomad4 subpopulation. Median coverage is 23. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 5 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KDM6A	NM_001291415.2 linkuse as main transcript	c.48_50dup	p.Ala16dup	inframe_insertion	1/30	ENST00000611820.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KDM6A	ENST00000611820.5 linkuse as main transcript	c.48_50dup	p.Ala16dup	inframe_insertion	1/30	1	NM_001291415.2	P4

Frequencies

GnomAD3 genomes

AF:

0.00576

AC:

638

AN:

110711

Hom.:

Cov.:

AF XY:

0.00477

AC XY:

159

AN XY:

33351

show subpopulations

Gnomad AFR

AF:

0.0197

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00227

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000373

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000171

Gnomad OTH

AF:

0.00269

GnomAD3 exomes

AF:

0.00151

AC:

249

AN:

165211

Hom.:

AF XY:

0.000860

AC XY:

AN XY:

58141

show subpopulations

Gnomad AFR exome

AF:

0.0202

Gnomad AMR exome

AF:

0.00117

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000550

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000842

Gnomad OTH exome

AF:

0.000243

GnomAD4 exome

AF:

0.000657

AC:

718

AN:

1093230

Hom.:

Cov.:

AF XY:

0.000530

AC XY:

191

AN XY:

360198

show subpopulations

Gnomad4 AFR exome

AF:

0.0210

Gnomad4 AMR exome

AF:

0.00143

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000744

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000524

Gnomad4 OTH exome

AF:

0.00144

GnomAD4 genome

AF:

0.00580

AC:

642

AN:

110759

Hom.:

Cov.:

AF XY:

0.00482

AC XY:

161

AN XY:

33409

show subpopulations

Gnomad4 AFR

AF:

0.0199

Gnomad4 AMR

AF:

0.00227

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000171

Gnomad4 OTH

AF:

0.00265

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -
Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	May 26, 2015	- -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -
Benign, criteria provided, single submitter	clinical testing	Genetic Services Laboratory, University of Chicago	Dec 27, 2018	- -

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

May 10, 2019

- -

Kabuki syndrome 2

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 29, 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