rs61751429
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Variant summary
Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_ModerateBP6_Very_StrongBS1BS2
The NM_001291415.2(KDM6A):c.1683+3G>A variant causes a splice donor region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00386 in 1,113,530 control chromosomes in the GnomAD database, including 7 homozygotes. There are 1,207 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.0027 ( 1 hom., 78 hem., cov: 22)
Exomes 𝑓: 0.0040 ( 6 hom. 1129 hem. )
Consequence
KDM6A
NM_001291415.2 splice_donor_region, intron
NM_001291415.2 splice_donor_region, intron
Scores
2
Splicing: ADA: 0.0001326
2
Clinical Significance
Conservation
PhyloP100: 0.965
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]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -18 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.34).
BP6
Variant X-45062751-G-A is Benign according to our data. Variant chrX-45062751-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 261406.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chrX-45062751-G-A is described in Lovd as [Likely_benign].
BS1
Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00274 (307/112215) while in subpopulation NFE AF= 0.00473 (252/53228). AF 95% confidence interval is 0.00425. There are 1 homozygotes in gnomad4. There are 78 alleles in male gnomad4 subpopulation. Median coverage is 22. This position pass quality control queck.
BS2
High Hemizygotes in GnomAd4 at 78 XL gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
KDM6A | NM_001291415.2 | c.1683+3G>A | splice_donor_region_variant, intron_variant | ENST00000611820.5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
KDM6A | ENST00000611820.5 | c.1683+3G>A | splice_donor_region_variant, intron_variant | 1 | NM_001291415.2 | P4 |
Frequencies
GnomAD3 genomes AF: 0.00274 AC: 307AN: 112161Hom.: 1 Cov.: 22 AF XY: 0.00227 AC XY: 78AN XY: 34319
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GnomAD3 exomes AF: 0.00254 AC: 460AN: 181089Hom.: 0 AF XY: 0.00270 AC XY: 178AN XY: 65817
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GnomAD4 exome AF: 0.00399 AC: 3991AN: 1001315Hom.: 6 Cov.: 20 AF XY: 0.00392 AC XY: 1129AN XY: 288221
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GnomAD4 genome AF: 0.00274 AC: 307AN: 112215Hom.: 1 Cov.: 22 AF XY: 0.00227 AC XY: 78AN XY: 34383
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:7
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:3
Likely benign, no assertion criteria provided | clinical testing | Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC) | - | - - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Sep 24, 2018 | - - |
Likely benign, no assertion criteria provided | clinical testing | Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center | - | - - |
not specified Benign:2
Likely benign, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Jun 18, 2018 | - - |
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Kabuki syndrome 2 Benign:2
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 29, 2024 | - - |
Benign, criteria provided, single submitter | clinical testing | ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories | Apr 15, 2022 | - - |
Computational scores
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Name
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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dbscSNV1_ADA
Benign
dbscSNV1_RF
Benign
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at