rs746959201
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 1P and 0B. PP3
The NM_000751.3(CHRND):c.647G>A(p.Arg216Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000112 in 1,613,888 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. R216W) 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 1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CHRND | NM_000751.3 | c.647G>A | p.Arg216Gln | missense_variant | 7/12 | ENST00000258385.8 | |
CHRND | NM_001256657.2 | c.602G>A | p.Arg201Gln | missense_variant | 6/11 | ||
CHRND | NM_001311196.2 | c.344G>A | p.Arg115Gln | missense_variant | 7/12 | ||
CHRND | NM_001311195.2 | c.238+1310G>A | intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CHRND | ENST00000258385.8 | c.647G>A | p.Arg216Gln | missense_variant | 7/12 | 1 | NM_000751.3 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000132 AC: 2AN: 152084Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000241 AC: 6AN: 249236Hom.: 0 AF XY: 0.0000148 AC XY: 2AN XY: 134916
GnomAD4 exome AF: 0.0000109 AC: 16AN: 1461804Hom.: 0 Cov.: 32 AF XY: 0.0000138 AC XY: 10AN XY: 727204
GnomAD4 genome ? AF: 0.0000132 AC: 2AN: 152084Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74298
ClinVar
Submissions by phenotype
Lethal multiple pterygium syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Mar 30, 2023 | ClinVar contains an entry for this variant (Variation ID: 579890). This variant has not been reported in the literature in individuals affected with CHRND-related conditions. This variant is present in population databases (rs746959201, gnomAD 0.02%). This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 216 of the CHRND protein (p.Arg216Gln). 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. 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