rs201005099
Variant summary
Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2
The NM_021267.5(CERS1):c.437G>A(p.Arg146Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00012 in 1,613,148 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 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. R146W) has been classified as Uncertain significance.
Frequency
Consequence
NM_021267.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -8 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
CERS1 | NM_021267.5 | c.437G>A | p.Arg146Gln | missense_variant | Exon 3 of 8 | ENST00000623882.4 | NP_067090.1 | |
GDF1 | NM_001492.6 | c.-886G>A | 5_prime_UTR_variant | Exon 3 of 8 | ENST00000247005.8 | NP_001483.3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
CERS1 | ENST00000623882.4 | c.437G>A | p.Arg146Gln | missense_variant | Exon 3 of 8 | 1 | NM_021267.5 | ENSP00000485308.1 | ||
GDF1 | ENST00000247005.8 | c.-886G>A | 5_prime_UTR_variant | Exon 3 of 8 | 1 | NM_001492.6 | ENSP00000247005.5 |
Frequencies
GnomAD3 genomes AF: 0.0000526 AC: 8AN: 152034Hom.: 0 Cov.: 31
GnomAD3 exomes AF: 0.000254 AC: 62AN: 244546Hom.: 1 AF XY: 0.000330 AC XY: 44AN XY: 133190
GnomAD4 exome AF: 0.000127 AC: 186AN: 1460996Hom.: 2 Cov.: 31 AF XY: 0.000176 AC XY: 128AN XY: 726756
GnomAD4 genome AF: 0.0000460 AC: 7AN: 152152Hom.: 0 Cov.: 31 AF XY: 0.0000403 AC XY: 3AN XY: 74386
ClinVar
Submissions by phenotype
Progressive myoclonic epilepsy type 8 Uncertain:1
This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 146 of the CERS1 protein (p.Arg146Gln). This variant is present in population databases (rs201005099, gnomAD 0.2%). This variant has not been reported in the literature in individuals affected with CERS1-related conditions. ClinVar contains an entry for this variant (Variation ID: 475371). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is not expected to disrupt CERS1 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. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at