rs200520898
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_014956.5(CEP164):c.4060G>A(p.Asp1354Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000199 in 1,614,164 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).
Frequency
Consequence
NM_014956.5 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 |
---|---|---|---|---|---|---|---|
CEP164 | NM_014956.5 | c.4060G>A | p.Asp1354Asn | missense_variant | 30/33 | ENST00000278935.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CEP164 | ENST00000278935.8 | c.4060G>A | p.Asp1354Asn | missense_variant | 30/33 | 1 | NM_014956.5 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.000223 AC: 34AN: 152170Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000257 AC: 64AN: 249106Hom.: 0 AF XY: 0.000334 AC XY: 45AN XY: 134928
GnomAD4 exome AF: 0.000198 AC: 290AN: 1461876Hom.: 1 Cov.: 37 AF XY: 0.000235 AC XY: 171AN XY: 727236
GnomAD4 genome ? AF: 0.000204 AC: 31AN: 152288Hom.: 0 Cov.: 32 AF XY: 0.000188 AC XY: 14AN XY: 74454
ClinVar
Submissions by phenotype
Nephronophthisis 15 Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jan 11, 2024 | This sequence change replaces aspartic acid, which is acidic and polar, with asparagine, which is neutral and polar, at codon 1354 of the CEP164 protein (p.Asp1354Asn). This variant is present in population databases (rs200520898, gnomAD 0.1%). 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: 569863). 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 CEP164 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 | Fulgent Genetics, Fulgent Genetics | May 23, 2022 | - - |
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Feb 11, 2022 | The c.4060G>A (p.D1354N) alteration is located in exon 30 (coding exon 28) of the CEP164 gene. This alteration results from a G to A substitution at nucleotide position 4060, causing the aspartic acid (D) at amino acid position 1354 to be replaced by an asparagine (N). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Nephronophthisis Uncertain:1
Uncertain significance, no assertion criteria provided | clinical testing | Sydney Genome Diagnostics, Children's Hospital Westmead | Oct 03, 2016 | This patient is homozygous for a variant of unknown clinical significance (VOUS), c.4060G>A p.(Asp1354Asn) in exon 30 of the CEP164 gene. To our knowledge, this variant has not been previously reported in the literature. This variant has been reported in dbSNP (rs200520898) and ESP with a minor allele frequency of 0.05% in a European American population. In silico analysis (Alamut Visual v2.4) using PolyPhen2, SIFT, Align GVGD and Mutation Taster all suggest that this variant does not affect protein function and is likely to be a non-pathogenic variant. Alamut Visual v2.4 also predicts this variant does not affect splicing. However, this analysis alone cannot be used to exclude pathogenicity. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at