4-165464579-C-T
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_001873.4(CPE):c.497C>T(p.Ala166Val) variant causes a missense change. The variant allele was found at a frequency of 0.00000932 in 1,608,634 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. A166T) has been classified as Uncertain significance.
Frequency
Consequence
NM_001873.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CPE | NM_001873.4 | c.497C>T | p.Ala166Val | missense_variant | 2/9 | ENST00000402744.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CPE | ENST00000402744.9 | c.497C>T | p.Ala166Val | missense_variant | 2/9 | 1 | NM_001873.4 | P1 | |
CPE | ENST00000511992.1 | c.161C>T | p.Ala54Val | missense_variant | 2/5 | 5 | |||
CPE | ENST00000431967.5 | c.161C>T | p.Ala54Val | missense_variant | 2/4 | 4 | |||
CPE | ENST00000513982.5 | c.161C>T | p.Ala54Val | missense_variant | 2/4 | 4 |
Frequencies
GnomAD3 genomes AF: 0.0000329 AC: 5AN: 152140Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000122 AC: 3AN: 246274Hom.: 0 AF XY: 0.0000150 AC XY: 2AN XY: 133064
GnomAD4 exome AF: 0.00000687 AC: 10AN: 1456494Hom.: 0 Cov.: 31 AF XY: 0.00000829 AC XY: 6AN XY: 724080
GnomAD4 genome AF: 0.0000329 AC: 5AN: 152140Hom.: 0 Cov.: 32 AF XY: 0.0000404 AC XY: 3AN XY: 74316
ClinVar
Submissions by phenotype
CPE-related disorder Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Mar 01, 2024 | The CPE c.497C>T variant is predicted to result in the amino acid substitution p.Ala166Val. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.019% of alleles in individuals of African descent in gnomAD. 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 | Nov 15, 2023 | The c.497C>T (p.A166V) alteration is located in exon 2 (coding exon 2) of the CPE gene. This alteration results from a C to T substitution at nucleotide position 497, causing the alanine (A) at amino acid position 166 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at