rs144206271
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The ENST00000278935.8(CEP164):c.548T>A(p.Met183Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000632 in 1,569,196 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 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. M183T) has been classified as Likely benign.
Frequency
Consequence
ENST00000278935.8 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 | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
CEP164 | NM_014956.5 | c.548T>A | p.Met183Lys | missense_variant | 6/33 | ENST00000278935.8 | NP_055771.4 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
CEP164 | ENST00000278935.8 | c.548T>A | p.Met183Lys | missense_variant | 6/33 | 1 | NM_014956.5 | ENSP00000278935 | P1 |
Frequencies
GnomAD3 genomes AF: 0.000447 AC: 68AN: 152204Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000608 AC: 125AN: 205506Hom.: 0 AF XY: 0.000682 AC XY: 75AN XY: 109898
GnomAD4 exome AF: 0.000653 AC: 925AN: 1416874Hom.: 1 Cov.: 31 AF XY: 0.000690 AC XY: 485AN XY: 702480
GnomAD4 genome AF: 0.000440 AC: 67AN: 152322Hom.: 0 Cov.: 32 AF XY: 0.000456 AC XY: 34AN XY: 74488
ClinVar
Submissions by phenotype
Nephronophthisis 15 Uncertain:2Other:1
Uncertain significance, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Feb 03, 2022 | - - |
not provided, no classification provided | phenotyping only | GenomeConnect - Invitae Patient Insights Network | - | Variant interpreted as Uncertain significance and reported on 08-21-2020 by Invitae. GenomeConnect-Invitae Patient Insights Network assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. Registry team members make no attempt to reinterpret the clinical significance of the variant. Phenotypic details are available under supporting information. - |
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Nov 01, 2022 | This sequence change replaces methionine, which is neutral and non-polar, with lysine, which is basic and polar, at codon 183 of the CEP164 protein (p.Met183Lys). This variant is present in population databases (rs144206271, 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 CEP164-related conditions. ClinVar contains an entry for this variant (Variation ID: 573184). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. 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. - |
CEP164-related disorder Uncertain:1
Uncertain significance, no assertion criteria provided | clinical testing | PreventionGenetics, part of Exact Sciences | Sep 03, 2024 | The CEP164 c.548T>A variant is predicted to result in the amino acid substitution p.Met183Lys. To our knowledge, this variant has not been reported in individuals with CEP164-associated disorders in the literature. This variant is reported in 0.14% of alleles in individuals of South Asian descent in gnomAD. Although we suspect that this variant may be benign, at this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. - |
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Apr 23, 2024 | The c.548T>A (p.M183K) alteration is located in exon 6 (coding exon 4) of the CEP164 gene. This alteration results from a T to A substitution at nucleotide position 548, causing the methionine (M) at amino acid position 183 to be replaced by a lysine (K). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | not provided | Breakthrough Genomics, Breakthrough Genomics | - | - - |
Retinal dystrophy Uncertain:1
Uncertain significance, no assertion criteria provided | clinical testing | Institute of Human Genetics, Univ. Regensburg, Univ. Regensburg | Jan 01, 2022 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at