rs1064796932
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 1P and 0B. PP2
The NM_001376.5(DYNC1H1):c.10682G>A(p.Arg3561His) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000682 in 1,613,956 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. R3561P) has been classified as Uncertain significance.
Frequency
Consequence
NM_001376.5 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 |
---|---|---|---|---|---|---|---|
DYNC1H1 | NM_001376.5 | c.10682G>A | p.Arg3561His | missense_variant | 56/78 | ENST00000360184.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DYNC1H1 | ENST00000360184.10 | c.10682G>A | p.Arg3561His | missense_variant | 56/78 | 1 | NM_001376.5 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00000657 AC: 1AN: 152214Hom.: 0 Cov.: 32
GnomAD4 exome AF: 0.00000684 AC: 10AN: 1461742Hom.: 0 Cov.: 31 AF XY: 0.00000688 AC XY: 5AN XY: 727184
GnomAD4 genome ? AF: 0.00000657 AC: 1AN: 152214Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74360
ClinVar
Submissions by phenotype
Charcot-Marie-Tooth disease axonal type 2O Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | May 28, 2022 | 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. This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 3561 of the DYNC1H1 protein (p.Arg3561His). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with DYNC1H1-related conditions. ClinVar contains an entry for this variant (Variation ID: 424360). 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 DYNC1H1 protein function. - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Mar 23, 2017 | The R3561H variant in the DYNC1H1 gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. The R3561H variant is not observed in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The R3561H variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. While this substitution occurs at a position that is conserved across species, in silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. We interpret R3561H as a variant of uncertain significance. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at