rs200671975
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PP3_Strong
The NM_000751.3(CHRND):c.1067C>T(p.Pro356Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000496 in 1,612,980 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. P356S) 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.1067C>T | p.Pro356Leu | missense_variant | 10/12 | ENST00000258385.8 | |
CHRND | NM_001256657.2 | c.1022C>T | p.Pro341Leu | missense_variant | 9/11 | ||
CHRND | NM_001311196.2 | c.764C>T | p.Pro255Leu | missense_variant | 10/12 | ||
CHRND | NM_001311195.2 | c.485C>T | p.Pro162Leu | missense_variant | 8/10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CHRND | ENST00000258385.8 | c.1067C>T | p.Pro356Leu | missense_variant | 10/12 | 1 | NM_000751.3 | P1 | |
CHRND | ENST00000543200.5 | c.1022C>T | p.Pro341Leu | missense_variant | 9/11 | 2 | |||
CHRND | ENST00000441621.6 | c.*249C>T | 3_prime_UTR_variant, NMD_transcript_variant | 9/11 | 5 | ||||
CHRND | ENST00000446616.1 | c.*708C>T | 3_prime_UTR_variant, NMD_transcript_variant | 10/12 | 3 |
Frequencies
GnomAD3 genomes ? AF: 0.000289 AC: 44AN: 152220Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.000104 AC: 26AN: 250268Hom.: 0 AF XY: 0.0000738 AC XY: 10AN XY: 135556
GnomAD4 exome AF: 0.0000246 AC: 36AN: 1460642Hom.: 0 Cov.: 32 AF XY: 0.0000234 AC XY: 17AN XY: 726648
GnomAD4 genome ? AF: 0.000289 AC: 44AN: 152338Hom.: 0 Cov.: 33 AF XY: 0.000309 AC XY: 23AN XY: 74492
ClinVar
Submissions by phenotype
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Aug 13, 2021 | The c.1067C>T (p.P356L) alteration is located in exon 10 (coding exon 10) of the CHRND gene. This alteration results from a C to T substitution at nucleotide position 1067, causing the proline (P) at amino acid position 356 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Lethal multiple pterygium syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Dec 15, 2023 | This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 356 of the CHRND protein (p.Pro356Leu). This variant is present in population databases (rs200671975, gnomAD 0.1%). 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: 466187). 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%. 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. - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Revvity Omics, Revvity | Oct 15, 2019 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at