X-45063635-A-G
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Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2
The NM_001291415.2(KDM6A):āc.1897A>Gā(p.Thr633Ala) variant causes a missense change. The variant allele was found at a frequency of 0.00114 in 1,208,652 control chromosomes in the GnomAD database, including 9 homozygotes. There are 363 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (ā ā ).
Frequency
Genomes: š 0.0058 ( 5 hom., 166 hem., cov: 22)
Exomes š: 0.00066 ( 4 hom. 197 hem. )
Consequence
KDM6A
NM_001291415.2 missense
NM_001291415.2 missense
Scores
1
3
7
Clinical Significance
Conservation
PhyloP100: 6.71
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 -20 ACMG points.
BP4
Computational evidence support a benign effect (MetaRNN=0.007016927).
BP6
Variant X-45063635-A-G is Benign according to our data. Variant chrX-45063635-A-G is described in ClinVar as [Benign]. Clinvar id is 261405.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chrX-45063635-A-G is described in Lovd as [Likely_benign].
BS1
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00585 (653/111626) while in subpopulation AFR AF= 0.02 (615/30687). AF 95% confidence interval is 0.0187. There are 5 homozygotes in gnomad4. There are 166 alleles in male gnomad4 subpopulation. Median coverage is 22. 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 | c.1897A>G | p.Thr633Ala | missense_variant | 17/30 | ENST00000611820.5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
KDM6A | ENST00000611820.5 | c.1897A>G | p.Thr633Ala | missense_variant | 17/30 | 1 | NM_001291415.2 | P4 |
Frequencies
GnomAD3 genomes AF: 0.00583 AC: 650AN: 111574Hom.: 5 Cov.: 22 AF XY: 0.00489 AC XY: 165AN XY: 33758
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GnomAD3 exomes AF: 0.00175 AC: 317AN: 181660Hom.: 2 AF XY: 0.00110 AC XY: 73AN XY: 66246
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GnomAD4 exome AF: 0.000657 AC: 721AN: 1097026Hom.: 4 Cov.: 30 AF XY: 0.000544 AC XY: 197AN XY: 362408
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GnomAD4 genome AF: 0.00585 AC: 653AN: 111626Hom.: 5 Cov.: 22 AF XY: 0.00491 AC XY: 166AN XY: 33820
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ClinVar
Significance: Benign
Submissions summary: Benign:4
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:2
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Benign, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Dec 27, 2018 | - - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | GeneDx | Sep 25, 2020 | - - |
Kabuki syndrome 2 Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 29, 2024 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Uncertain
DANN
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D;D;D;D;D
MetaRNN
Benign
T;T;T;T;T
MetaSVM
Benign
T
MutationTaster
Benign
D;D;D;D
PrimateAI
Uncertain
T
Sift4G
Benign
T;T;T;T;T
Polyphen
0.82
.;.;.;.;P
Vest4
MVP
MPC
0.11
ClinPred
T
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at