2-232534120-C-T
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PP3_Moderate
The NM_000751.3(CHRND):c.1237C>T(p.Arg413Cys) variant causes a missense change. The variant allele was found at a frequency of 0.0000118 in 1,613,972 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. R413H) has been classified as Uncertain significance.
Frequency
Consequence
NM_000751.3 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 |
---|---|---|---|---|---|---|---|
CHRND | NM_000751.3 | c.1237C>T | p.Arg413Cys | missense_variant | 10/12 | ENST00000258385.8 | |
CHRND | NM_001256657.2 | c.1192C>T | p.Arg398Cys | missense_variant | 9/11 | ||
CHRND | NM_001311196.2 | c.934C>T | p.Arg312Cys | missense_variant | 10/12 | ||
CHRND | NM_001311195.2 | c.655C>T | p.Arg219Cys | missense_variant | 8/10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CHRND | ENST00000258385.8 | c.1237C>T | p.Arg413Cys | missense_variant | 10/12 | 1 | NM_000751.3 | P1 | |
CHRND | ENST00000543200.5 | c.1192C>T | p.Arg398Cys | missense_variant | 9/11 | 2 | |||
CHRND | ENST00000441621.6 | c.*419C>T | 3_prime_UTR_variant, NMD_transcript_variant | 9/11 | 5 | ||||
CHRND | ENST00000446616.1 | c.*878C>T | 3_prime_UTR_variant, NMD_transcript_variant | 10/12 | 3 |
Frequencies
GnomAD3 genomes AF: 0.0000131 AC: 2AN: 152222Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251256Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135884
GnomAD4 exome AF: 0.0000116 AC: 17AN: 1461750Hom.: 0 Cov.: 32 AF XY: 0.00000550 AC XY: 4AN XY: 727188
GnomAD4 genome AF: 0.0000131 AC: 2AN: 152222Hom.: 0 Cov.: 33 AF XY: 0.0000134 AC XY: 1AN XY: 74372
ClinVar
Submissions by phenotype
Lethal multiple pterygium syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Nov 18, 2023 | This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 413 of the CHRND protein (p.Arg413Cys). This variant is present in population databases (no rsID available, gnomAD 0.003%). 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: 575523). 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 95%. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. 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