rs201172776
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_001194998.2(CEP152):āc.3085A>Gā(p.Met1029Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000979 in 1,614,036 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ā ). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. M1029T) has been classified as Uncertain significance.
Frequency
Consequence
NM_001194998.2 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CEP152 | NM_001194998.2 | c.3085A>G | p.Met1029Val | missense_variant | 20/27 | ENST00000380950.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CEP152 | ENST00000380950.7 | c.3085A>G | p.Met1029Val | missense_variant | 20/27 | 1 | NM_001194998.2 | A2 | |
CEP152 | ENST00000399334.7 | c.3085A>G | p.Met1029Val | missense_variant | 20/26 | 1 | P2 | ||
CEP152 | ENST00000325747.9 | c.2806A>G | p.Met936Val | missense_variant | 19/25 | 1 | A2 |
Frequencies
GnomAD3 genomes ? AF: 0.000112 AC: 17AN: 152226Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000641 AC: 16AN: 249422Hom.: 0 AF XY: 0.0000739 AC XY: 10AN XY: 135318
GnomAD4 exome AF: 0.0000965 AC: 141AN: 1461810Hom.: 0 Cov.: 32 AF XY: 0.000117 AC XY: 85AN XY: 727208
GnomAD4 genome ? AF: 0.000112 AC: 17AN: 152226Hom.: 0 Cov.: 32 AF XY: 0.0000941 AC XY: 7AN XY: 74382
ClinVar
Submissions by phenotype
Microcephaly 9, primary, autosomal recessive Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Jan 28, 2014 | - - |
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Sep 16, 2021 | The c.3085A>G (p.M1029V) alteration is located in exon 20 (coding exon 19) of the CEP152 gene. This alteration results from a A to G substitution at nucleotide position 3085, causing the methionine (M) at amino acid position 1029 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jul 16, 2022 | This sequence change replaces methionine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 1029 of the CEP152 protein (p.Met1029Val). This variant is present in population databases (rs201172776, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with CEP152-related conditions. ClinVar contains an entry for this variant (Variation ID: 158251). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The valine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. 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. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at