X-45076679-CT-C

Variant names:

• chrX-45076679-CT-C
• rs10605935
• NM_001291415.2:c.2859-5delT

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP6_Very_Strong

The NM_001291415.2(KDM6A):​c.2859-5delT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.78 (22303 hom., 12450 hem., cov: 0)
  • Exomes 𝑓: 0.57 (38906 hom. 46201 hem.)
  • Failed GnomAD Quality Control
• Consequence: KDM6A NM_001291415.2 splice_region, intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:8
• Conservation: PhyloP100: -0.699

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]

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BP6: Variant X-45076679-CT-C is Benign according to our data. Variant chrX-45076679-CT-C is described in ClinVar as [Benign]. Clinvar id is 281158.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chrX-45076679-CT-C is described in Lovd as [Benign]. Variant chrX-45076679-CT-C is described in Lovd as [Likely_benign].

Transcripts

RefSeq

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

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.775 AC: 68346 AN: 88152 Hom.: 22316 Cov.: 0 AF XY: 0.748 AC XY: 12437 AN XY: 16622

Gnomad AFR AF: 0.588

Gnomad AMI AF: 0.961

Gnomad AMR AF: 0.887

Gnomad ASJ AF: 0.852

Gnomad EAS AF: 0.615

Gnomad SAS AF: 0.730

Gnomad FIN AF: 0.794

Gnomad MID AF: 0.870

Gnomad NFE AF: 0.863

Gnomad OTH AF: 0.798

GnomAD3 exomes AF: 0.532 AC: 42237 AN: 79362 Hom.: 2620 AF XY: 0.663 AC XY: 4630 AN XY: 6988

Gnomad AFR exome AF: 0.473

Gnomad AMR exome AF: 0.549

Gnomad ASJ exome AF: 0.534

Gnomad EAS exome AF: 0.474

Gnomad SAS exome AF: 0.501

Gnomad FIN exome AF: 0.560

Gnomad NFE exome AF: 0.552

Gnomad OTH exome AF: 0.531

GnomAD4 exome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.565 AC: 337605 AN: 597170 Hom.: 38906 Cov.: 0 AF XY: 0.602 AC XY: 46201 AN XY: 76766

Gnomad4 AFR exome AF: 0.441

Gnomad4 AMR exome AF: 0.549

Gnomad4 ASJ exome AF: 0.542

Gnomad4 EAS exome AF: 0.421

Gnomad4 SAS exome AF: 0.462

Gnomad4 FIN exome AF: 0.529

Gnomad4 NFE exome AF: 0.586

Gnomad4 OTH exome AF: 0.549

GnomAD4 genome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.775 AC: 68334 AN: 88156 Hom.: 22303 Cov.: 0 AF XY: 0.748 AC XY: 12450 AN XY: 16642

Gnomad4 AFR AF: 0.588

Gnomad4 AMR AF: 0.887

Gnomad4 ASJ AF: 0.852

Gnomad4 EAS AF: 0.614

Gnomad4 SAS AF: 0.730

Gnomad4 FIN AF: 0.794

Gnomad4 NFE AF: 0.863

Gnomad4 OTH AF: 0.793

ClinVar

Significance: Benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:4

Oct 21, 2015

Eurofins Ntd Llc (ga)

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

-

Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Jan 24, 2024

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is classified as Benign based on local population frequency. This variant was detected in 33% of patients studied by a panel of primary immunodeficiencies. Number of patients: 31. Only high quality variants are reported. -

not provided Benign:2

Aug 10, 2019

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

Genome Diagnostics Laboratory, University Medical Center Utrecht

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Kabuki syndrome 2 Benign:2

Aug 19, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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

Other links and lift over

dbSNP: rs10605935; hg19: chrX-44935924;