rs143955805
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Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2
The NM_004187.5(KDM5C):āc.2823A>Gā(p.Ser941=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00121 in 1,207,911 control chromosomes in the GnomAD database, including 2 homozygotes. There are 477 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 0.0014 ( 1 hom., 53 hem., cov: 25)
Exomes š: 0.0012 ( 1 hom. 424 hem. )
Consequence
KDM5C
NM_004187.5 synonymous
NM_004187.5 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.00400
Genes affected
KDM5C (HGNC:11114): (lysine demethylase 5C) This gene is a member of the SMCY homolog family and encodes a protein with one ARID domain, one JmjC domain, one JmjN domain and two PHD-type zinc fingers. The DNA-binding motifs suggest this protein is involved in the regulation of transcription and chromatin remodeling. Mutations in this gene have been associated with X-linked cognitive disability. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Apr 2009]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -21 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.8).
BP6
?
Variant X-53196844-T-C is Benign according to our data. Variant chrX-53196844-T-C is described in ClinVar as [Benign]. Clinvar id is 211248.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chrX-53196844-T-C is described in Lovd as [Benign].
BP7
?
Synonymous conserved (PhyloP=-0.004 with no splicing effect.
BS1
?
Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.00138 (157/113510) while in subpopulation AMR AF= 0.0034 (37/10880). AF 95% confidence interval is 0.00254. There are 1 homozygotes in gnomad4. There are 53 alleles in male gnomad4 subpopulation. Median coverage is 25. This position pass quality control queck.
BS2
?
High Hemizygotes in GnomAd4 at 53 XL gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
KDM5C | NM_004187.5 | c.2823A>G | p.Ser941= | synonymous_variant | 19/26 | ENST00000375401.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
KDM5C | ENST00000375401.8 | c.2823A>G | p.Ser941= | synonymous_variant | 19/26 | 1 | NM_004187.5 | P5 |
Frequencies
GnomAD3 genomes ? AF: 0.00138 AC: 157AN: 113459Hom.: 1 Cov.: 25 AF XY: 0.00149 AC XY: 53AN XY: 35593
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GnomAD3 exomes AF: 0.00131 AC: 224AN: 171337Hom.: 0 AF XY: 0.00145 AC XY: 84AN XY: 57875
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GnomAD4 exome AF: 0.00119 AC: 1306AN: 1094401Hom.: 1 Cov.: 32 AF XY: 0.00118 AC XY: 424AN XY: 360161
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GnomAD4 genome ? AF: 0.00138 AC: 157AN: 113510Hom.: 1 Cov.: 25 AF XY: 0.00149 AC XY: 53AN XY: 35654
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ClinVar
Significance: Benign
Submissions summary: Benign:7
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:4
Benign, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Aug 24, 2015 | - - |
Benign, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Mar 02, 2016 | - - |
Benign, no assertion criteria provided | clinical testing | Genome Diagnostics Laboratory, University Medical Center Utrecht | - | - - |
Benign, no assertion criteria provided | clinical testing | Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center | - | - - |
Spastic paraplegia Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 29, 2024 | - - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | GeneDx | Oct 02, 2019 | - - |
KDM5C-related disorder Benign:1
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Apr 24, 2019 | This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
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Name
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
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