chrX-44873574-T-TCGCTACCGCCGC
Variant summary
Our verdict is Likely benign. Variant got -1 ACMG points: 0P and 1B. BP3
The NM_001291415.2(KDM6A):c.28_39dup(p.Thr10_Ala13dup) variant causes a inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000302 in 1,092,546 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 10 hemizygotes in GnomAD. Variant has been reported in ClinVar as Uncertain significance (★★). Synonymous variant affecting the same amino acid position (i.e. L8L) has been classified as Likely benign.
Frequency
Consequence
NM_001291415.2 inframe_insertion
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
KDM6A | NM_001291415.2 | c.28_39dup | p.Thr10_Ala13dup | inframe_insertion | 1/30 | ENST00000611820.5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
KDM6A | ENST00000611820.5 | c.28_39dup | p.Thr10_Ala13dup | inframe_insertion | 1/30 | 1 | NM_001291415.2 | P4 |
Frequencies
GnomAD3 genomes ? AF: 0.0000192 AC: 2AN: 104047Hom.: 0 Cov.: 23 AF XY: 0.0000336 AC XY: 1AN XY: 29775
GnomAD3 exomes AF: 0.00000602 AC: 1AN: 166020Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 59016
GnomAD4 exome AF: 0.0000302 AC: 33AN: 1092546Hom.: 0 Cov.: 32 AF XY: 0.0000278 AC XY: 10AN XY: 359818
GnomAD4 genome ? Data not reliable, filtered out with message: AS_VQSR AF: 0.0000192 AC: 2AN: 104047Hom.: 0 Cov.: 23 AF XY: 0.0000336 AC XY: 1AN XY: 29775
ClinVar
Submissions by phenotype
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Dec 20, 2023 | The c.28_39dupACCGCCGCCGCT (p.T10_A13dup) alteration is located in exon 1 (coding exon 1) of the KDM6A gene. The alteration consists of an in-frame duplication of 12 nucleotides from position 28 to 39, resulting in the duplication of <NA> residues. Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
KDM6A-related disorder Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Oct 25, 2022 | The KDM6A c.28_39dup12 variant is predicted to result in an in-frame duplication (p.Thr10 Ala13dup). To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.0068% of alleles in individuals of European (Finnish) descent in gnomAD (http://gnomad.broadinstitute.org/variant/X-44732820-T-TCGCTACCGCCGC). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. - |
Kabuki syndrome 2 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | May 27, 2023 | In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. ClinVar contains an entry for this variant (Variation ID: 1383579). This variant has not been reported in the literature in individuals affected with KDM6A-related conditions. This variant is present in population databases (no rsID available, gnomAD 0.007%). This variant, c.28_39dup, results in the insertion of 4 amino acid(s) of the KDM6A protein (p.Thr10_Ala13dup), but otherwise preserves the integrity of the reading frame. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at