rs121909509
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PP3_Strong
The NM_000751.3(CHRND):c.236T>A(p.Ile79Lys) variant causes a missense change. The variant allele was found at a frequency of 0.00000496 in 1,613,168 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. I79T) has been classified as Uncertain significance.
Frequency
Consequence
NM_000751.3 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Uncertain_significance. Variant got 4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CHRND | NM_000751.3 | c.236T>A | p.Ile79Lys | missense_variant | 3/12 | ENST00000258385.8 | |
CHRND | NM_001311195.2 | c.-36T>A | 5_prime_UTR_variant | 3/10 | |||
CHRND | NM_001311196.2 | c.-36T>A | 5_prime_UTR_variant | 3/12 | |||
CHRND | NM_001256657.2 | c.198+764T>A | intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CHRND | ENST00000258385.8 | c.236T>A | p.Ile79Lys | missense_variant | 3/12 | 1 | NM_000751.3 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00000658 AC: 1AN: 152002Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251286Hom.: 0 AF XY: 0.00000736 AC XY: 1AN XY: 135834
GnomAD4 exome AF: 0.00000479 AC: 7AN: 1461166Hom.: 0 Cov.: 31 AF XY: 0.00000688 AC XY: 5AN XY: 726946
GnomAD4 genome ? AF: 0.00000658 AC: 1AN: 152002Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0AN XY: 74244
ClinVar
Submissions by phenotype
Congenital myasthenic syndrome 3B Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | May 01, 2008 | - - |
Lethal multiple pterygium syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jan 17, 2024 | This sequence change replaces isoleucine, which is neutral and non-polar, with lysine, which is basic and polar, at codon 79 of the CHRND protein (p.Ile79Lys). This variant is present in population databases (rs121909509, gnomAD 0.002%). This missense change has been observed in individual(s) with clinical features of autosomal recessive CHRND-related conditions (PMID: 18398509, 29399782). This variant is also known as I58K. ClinVar contains an entry for this variant (Variation ID: 18365). 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 expected to disrupt CHRND protein function with a positive predictive value of 80%. Experimental studies have shown that this missense change affects CHRND function (PMID: 18398509). 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