X-45076726-G-C
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Variant summary
Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_ModerateBP6_ModerateBS1BS2
The NM_001291415.2(KDM6A):āc.2888G>Cā(p.Ser963Thr) variant causes a missense change. The variant allele was found at a frequency of 0.0000501 in 1,157,800 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 27 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (ā ).
Frequency
Genomes: š 0.000041 ( 0 hom., 1 hem., cov: 20)
Exomes š: 0.000051 ( 0 hom. 26 hem. )
Consequence
KDM6A
NM_001291415.2 missense
NM_001291415.2 missense
Scores
2
5
10
Clinical Significance
Conservation
PhyloP100: 6.39
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 -12 ACMG points.
BP4
Computational evidence support a benign effect (MetaRNN=0.10689333).
BP6
Variant X-45076726-G-C is Benign according to our data. Variant chrX-45076726-G-C is described in ClinVar as [Benign]. Clinvar id is 134598.Status of the report is criteria_provided_single_submitter, 1 stars.
BS1
Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.0000408 (4/97981) while in subpopulation SAS AF= 0.000961 (2/2082). AF 95% confidence interval is 0.00017. There are 0 homozygotes in gnomad4. There are 1 alleles in male gnomad4 subpopulation. Median coverage is 20. This position pass quality control queck.
BS2
High Hemizygotes in GnomAdExome4 at 26 XL gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
KDM6A | NM_001291415.2 | c.2888G>C | p.Ser963Thr | missense_variant | 19/30 | ENST00000611820.5 | NP_001278344.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
KDM6A | ENST00000611820.5 | c.2888G>C | p.Ser963Thr | missense_variant | 19/30 | 1 | NM_001291415.2 | ENSP00000483595.2 |
Frequencies
GnomAD3 genomes AF: 0.0000408 AC: 4AN: 97949Hom.: 0 Cov.: 20 AF XY: 0.0000404 AC XY: 1AN XY: 24735
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GnomAD3 exomes AF: 0.0000659 AC: 12AN: 181991Hom.: 0 AF XY: 0.000105 AC XY: 7AN XY: 66755
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GnomAD4 exome AF: 0.0000510 AC: 54AN: 1059819Hom.: 0 Cov.: 26 AF XY: 0.0000780 AC XY: 26AN XY: 333487
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GnomAD4 genome AF: 0.0000408 AC: 4AN: 97981Hom.: 0 Cov.: 20 AF XY: 0.0000404 AC XY: 1AN XY: 24767
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ClinVar
Significance: Benign
Submissions summary: Benign:2Other:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
KDM6A-related disorder Benign:1
Likely benign, no assertion criteria provided | clinical testing | PreventionGenetics, part of Exact Sciences | Sep 14, 2021 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Kabuki syndrome 2 Benign:1
Benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Nov 14, 2023 | - - |
not specified Other:1
not provided, no classification provided | reference population | ITMI | Sep 19, 2013 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Uncertain
DANN
Uncertain
DEOGEN2
Benign
.;T;.;T;T
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D;D;D;D;D
M_CAP
Pathogenic
D
MetaRNN
Benign
T;T;T;T;T
MetaSVM
Uncertain
D
MutationAssessor
Benign
.;.;.;.;L
PrimateAI
Uncertain
T
PROVEAN
Benign
.;.;.;.;N
REVEL
Uncertain
Sift
Benign
.;.;.;.;T
Sift4G
Benign
T;T;T;T;T
Polyphen
0.86
.;.;.;.;P
Vest4
MVP
MPC
0.10
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