rs748108743
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate
The NM_000751.3(CHRND):c.1088G>A(p.Arg363His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000217 in 1,613,426 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 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. R363P) has been classified as Uncertain significance.
Frequency
Consequence
NM_000751.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CHRND | NM_000751.3 | c.1088G>A | p.Arg363His | missense_variant | 10/12 | ENST00000258385.8 | |
CHRND | NM_001256657.2 | c.1043G>A | p.Arg348His | missense_variant | 9/11 | ||
CHRND | NM_001311196.2 | c.785G>A | p.Arg262His | missense_variant | 10/12 | ||
CHRND | NM_001311195.2 | c.506G>A | p.Arg169His | missense_variant | 8/10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CHRND | ENST00000258385.8 | c.1088G>A | p.Arg363His | missense_variant | 10/12 | 1 | NM_000751.3 | P1 | |
CHRND | ENST00000543200.5 | c.1043G>A | p.Arg348His | missense_variant | 9/11 | 2 | |||
CHRND | ENST00000441621.6 | c.*270G>A | 3_prime_UTR_variant, NMD_transcript_variant | 9/11 | 5 | ||||
CHRND | ENST00000446616.1 | c.*729G>A | 3_prime_UTR_variant, NMD_transcript_variant | 10/12 | 3 |
Frequencies
GnomAD3 genomes ? AF: 0.00000657 AC: 1AN: 152196Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.00000797 AC: 2AN: 250872Hom.: 0 AF XY: 0.0000147 AC XY: 2AN XY: 135756
GnomAD4 exome AF: 0.0000233 AC: 34AN: 1461230Hom.: 0 Cov.: 32 AF XY: 0.0000275 AC XY: 20AN XY: 726916
GnomAD4 genome ? AF: 0.00000657 AC: 1AN: 152196Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0AN XY: 74348
ClinVar
Submissions by phenotype
Lethal multiple pterygium syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | May 05, 2023 | This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 363 of the CHRND protein (p.Arg363His). This variant is present in population databases (rs748108743, gnomAD 0.007%). 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. 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. ClinVar contains an entry for this variant (Variation ID: 466188). This variant has not been reported in the literature in individuals affected with CHRND-related conditions. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at