rs150399616
Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2BP4_StrongBS1_Supporting
The NM_014679.5(CEP57):c.572T>A(p.Leu191His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0007 in 1,613,964 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).
Frequency
Consequence
NM_014679.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CEP57 | NM_014679.5 | c.572T>A | p.Leu191His | missense_variant | 5/11 | ENST00000325542.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CEP57 | ENST00000325542.10 | c.572T>A | p.Leu191His | missense_variant | 5/11 | 1 | NM_014679.5 |
Frequencies
GnomAD3 genomes ? AF: 0.000460 AC: 70AN: 152166Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000533 AC: 134AN: 251426Hom.: 0 AF XY: 0.000523 AC XY: 71AN XY: 135874
GnomAD4 exome AF: 0.000725 AC: 1059AN: 1461680Hom.: 1 Cov.: 30 AF XY: 0.000703 AC XY: 511AN XY: 727142
GnomAD4 genome ? AF: 0.000460 AC: 70AN: 152284Hom.: 0 Cov.: 32 AF XY: 0.000322 AC XY: 24AN XY: 74466
ClinVar
Submissions by phenotype
Mosaic variegated aneuploidy syndrome 2 Uncertain:3
Uncertain significance, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Oct 31, 2018 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Dec 17, 2023 | This sequence change replaces leucine, which is neutral and non-polar, with histidine, which is basic and polar, at codon 191 of the CEP57 protein (p.Leu191His). This variant is present in population databases (rs150399616, gnomAD 0.1%), and has an allele count higher than expected for a pathogenic variant. This variant has not been reported in the literature in individuals affected with CEP57-related conditions. ClinVar contains an entry for this variant (Variation ID: 408446). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt CEP57 protein function with a negative predictive value of 80%. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. - |
Uncertain significance, criteria provided, single submitter | clinical testing | MGZ Medical Genetics Center | May 24, 2022 | - - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Institute for Clinical Genetics, University Hospital TU Dresden, University Hospital TU Dresden | Nov 03, 2021 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at