2-232535158-G-T
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3
The NM_000751.3(CHRND):c.1400G>T(p.Arg467Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000248 in 1,614,042 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic 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. R467H) has been classified as Likely benign.
Frequency
Consequence
NM_000751.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
CHRND | NM_000751.3 | c.1400G>T | p.Arg467Leu | missense_variant | Exon 12 of 12 | ENST00000258385.8 | NP_000742.1 | |
CHRND | NM_001256657.2 | c.1355G>T | p.Arg452Leu | missense_variant | Exon 11 of 11 | NP_001243586.1 | ||
CHRND | NM_001311196.2 | c.1097G>T | p.Arg366Leu | missense_variant | Exon 12 of 12 | NP_001298125.1 | ||
CHRND | NM_001311195.2 | c.818G>T | p.Arg273Leu | missense_variant | Exon 10 of 10 | NP_001298124.1 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152222Hom.: 0 Cov.: 33
GnomAD4 exome AF: 0.00000205 AC: 3AN: 1461820Hom.: 0 Cov.: 32 AF XY: 0.00000275 AC XY: 2AN XY: 727230
GnomAD4 genome AF: 0.00000657 AC: 1AN: 152222Hom.: 0 Cov.: 33 AF XY: 0.0000134 AC XY: 1AN XY: 74372
ClinVar
Submissions by phenotype
Lethal multiple pterygium syndrome Uncertain:2
This sequence change replaces arginine, which is basic and polar, with leucine, which is neutral and non-polar, at codon 467 of the CHRND protein (p.Arg467Leu). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with CHRND-related conditions. ClinVar contains an entry for this variant (Variation ID: 1033119). 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 CHRND 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. -
This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868]. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at