chrX-53193001-G-A
Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 1P and 6B. PP2BP4_ModerateBS2
The NM_004187.5(KDM5C):c.4649C>T(p.Pro1550Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000262 in 1,181,892 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 9 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P1550S) has been classified as Uncertain significance.
Frequency
Consequence
NM_004187.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -5 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
KDM5C | NM_004187.5 | c.4649C>T | p.Pro1550Leu | missense_variant | 26/26 | ENST00000375401.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
KDM5C | ENST00000375401.8 | c.4649C>T | p.Pro1550Leu | missense_variant | 26/26 | 1 | NM_004187.5 | P5 |
Frequencies
GnomAD3 genomes AF: 0.0000184 AC: 2AN: 108876Hom.: 0 Cov.: 20 AF XY: 0.00 AC XY: 0AN XY: 31174
GnomAD3 exomes AF: 0.0000127 AC: 2AN: 157859Hom.: 0 AF XY: 0.0000196 AC XY: 1AN XY: 50991
GnomAD4 exome AF: 0.0000270 AC: 29AN: 1073016Hom.: 0 Cov.: 33 AF XY: 0.0000259 AC XY: 9AN XY: 347638
GnomAD4 genome AF: 0.0000184 AC: 2AN: 108876Hom.: 0 Cov.: 20 AF XY: 0.00 AC XY: 0AN XY: 31174
ClinVar
Submissions by phenotype
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Feb 07, 2018 | The p.P1550L variant (also known as c.4649C>T), located in coding exon 26 of the KDM5C gene, results from a C to T substitution at nucleotide position 4649. The proline at codon 1550 is replaced by leucine, an amino acid with similar properties. This amino acid position is not well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at