X-53192837-G-T
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2
The NM_004187.5(KDM5C):c.*130C>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000809 in 1,088,077 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 38 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 0.000020 ( 0 hom., 1 hem., cov: 19)
Exomes 𝑓: 0.000087 ( 0 hom. 37 hem. )
Consequence
KDM5C
NM_004187.5 3_prime_UTR
NM_004187.5 3_prime_UTR
Scores
2
Splicing: ADA: 0.00003729
2
Clinical Significance
Conservation
PhyloP100: 0.601
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 -20 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.84).
BP6
?
Variant X-53192837-G-T is Benign according to our data. Variant chrX-53192837-G-T is described in ClinVar as [Likely_benign]. Clinvar id is 2579094.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chrX-53192837-G-T is described in Lovd as [Likely_benign].
BS1
?
Variant frequency is greater than expected in population sas. gnomad4_exome allele frequency = 0.0000868 (86/990366) while in subpopulation SAS AF= 0.00167 (76/45551). AF 95% confidence interval is 0.00137. There are 0 homozygotes in gnomad4_exome. There are 37 alleles in male gnomad4_exome subpopulation. Median coverage is 21. This position pass quality control queck.
BS2
?
High Hemizygotes in GnomAdExome at 13 XL gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
KDM5C | NM_004187.5 | c.*130C>A | 3_prime_UTR_variant | 26/26 | ENST00000375401.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
KDM5C | ENST00000375401.8 | c.*130C>A | 3_prime_UTR_variant | 26/26 | 1 | NM_004187.5 | P5 |
Frequencies
GnomAD3 genomes ? AF: 0.0000205 AC: 2AN: 97655Hom.: 0 Cov.: 19 AF XY: 0.0000452 AC XY: 1AN XY: 22127
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GnomAD3 exomes AF: 0.000260 AC: 26AN: 100100Hom.: 0 AF XY: 0.000524 AC XY: 13AN XY: 24792
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GnomAD4 exome AF: 0.0000868 AC: 86AN: 990366Hom.: 0 Cov.: 21 AF XY: 0.000125 AC XY: 37AN XY: 296036
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ClinVar
Significance: Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Jul 01, 2023 | KDM5C: BP4, BP7, BS2 - |
KDM5C-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Apr 26, 2019 | 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). - |
Computational scores
Source:
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