Variant X-45076679-CTTT-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBS1BS2

The NM_001291415.2(KDM6A):c.2859-7_2859-5delTTT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00178 in 805,245 control chromosomes in the GnomAD database, including 2 homozygotes. There are 23 hemizygotes in GnomAD. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.00016 ( 0 hom., 2 hem., cov: 0)

Exomes 𝑓: 0.0020 ( 2 hom. 21 hem. )

Consequence

KDM6A
NM_001291415.2 splice_region, intron

Scores

Not classified

Clinical Significance

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-CTTT-C is Benign according to our data. Variant chrX-45076679-CTTT-C is described in ClinVar as [Benign]. Clinvar id is 194885.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 = 0.000158 (14/88378) while in subpopulation EAS AF= 0.00208 (6/2888). AF 95% confidence interval is 0.000904. There are 0 homozygotes in gnomad4. There are 2 alleles in male gnomad4 subpopulation. Median coverage is 0. This position pass quality control queck.

BS2

High Hemizygotes in GnomAd4 at 2 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KDM6A	NM_001291415.2 link	c.2859-7_2859-5delTTT		splice_region_variant, intron_variant		ENST00000611820.5	NP_001278344.1	A0A087X0R0B7ZKN5Q86TD1B7ZKN6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KDM6A	ENST00000611820.5 link	c.2859-7_2859-5delTTT		splice_region_variant, intron_variant		1	NM_001291415.2	ENSP00000483595.2		A0A087X0R0

Frequencies

GnomAD3 genomes

AF:

0.000158

AC:

AN:

88373

Hom.:

Cov.:

AF XY:

0.000119

AC XY:

AN XY:

16775

show subpopulations

Gnomad AFR

AF:

0.000122

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00207

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000793

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000667

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00386

AC:

306

AN:

79362

Hom.:

AF XY:

0.000716

AC XY:

AN XY:

6988

show subpopulations

Gnomad AFR exome

AF:

0.000781

Gnomad AMR exome

AF:

0.00196

Gnomad ASJ exome

AF:

0.00159

Gnomad EAS exome

AF:

0.0140

Gnomad SAS exome

AF:

0.00618

Gnomad FIN exome

AF:

0.00306

Gnomad NFE exome

AF:

0.00305

Gnomad OTH exome

AF:

0.00358

GnomAD4 exome

AF:

0.00198

AC:

1417

AN:

716867

Hom.:

AF XY:

0.000105

AC XY:

AN XY:

199911

show subpopulations

Gnomad4 AFR exome

AF:

0.00123

Gnomad4 AMR exome

AF:

0.00115

Gnomad4 ASJ exome

AF:

0.00110

Gnomad4 EAS exome

AF:

0.00866

Gnomad4 SAS exome

AF:

0.00262

Gnomad4 FIN exome

AF:

0.00211

Gnomad4 NFE exome

AF:

0.00169

Gnomad4 OTH exome

AF:

0.00256

GnomAD4 genome

AF:

0.000158

AC:

AN:

88378

Hom.:

Cov.:

AF XY:

0.000119

AC XY:

AN XY:

16796

show subpopulations

Gnomad4 AFR

AF:

0.000122

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00208

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000793

Gnomad4 NFE

AF:

0.0000667

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0111

Hom.:

1920

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Eurofins Ntd Llc (ga)

Dec 10, 2014

- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics

May 10, 2016

- -

Kabuki syndrome 2

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jul 19, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.070

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