rs763724110
Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 1P and 6B. PP2BP4_ModerateBS2
The NM_001376.5(DYNC1H1):āc.13286A>Gā(p.Gln4429Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000118 in 1,614,146 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ā ). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. Q4429E) has been classified as Uncertain significance.
Frequency
Consequence
NM_001376.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -5 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DYNC1H1 | NM_001376.5 | c.13286A>G | p.Gln4429Arg | missense_variant | 74/78 | ENST00000360184.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DYNC1H1 | ENST00000360184.10 | c.13286A>G | p.Gln4429Arg | missense_variant | 74/78 | 1 | NM_001376.5 | P1 | |
ENST00000553701.1 | n.346+1862T>C | intron_variant, non_coding_transcript_variant | 3 |
Frequencies
GnomAD3 genomes ? AF: 0.00000657 AC: 1AN: 152264Hom.: 0 Cov.: 31
GnomAD3 exomes AF: 0.0000119 AC: 3AN: 251482Hom.: 0 AF XY: 0.00000736 AC XY: 1AN XY: 135920
GnomAD4 exome AF: 0.0000123 AC: 18AN: 1461882Hom.: 0 Cov.: 31 AF XY: 0.0000151 AC XY: 11AN XY: 727242
GnomAD4 genome ? AF: 0.00000657 AC: 1AN: 152264Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0AN XY: 74396
ClinVar
Submissions by phenotype
Charcot-Marie-Tooth disease axonal type 2O Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Feb 28, 2019 | In summary, this variant is a rare missense change that is not predicted to affect protein function. There is no indication that it causes disease, but the available evidence is currently insufficient to prove that conclusively. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies. This variant is present in population databases (rs763724110, ExAC 0.01%) but has not been reported in the literature in individuals with a DYNC1H1-related disease. ClinVar contains an entry for this variant (Variation ID: 245792). This sequence change replaces glutamine with arginine at codon 4429 of the DYNC1H1 protein (p.Gln4429Arg). The glutamine residue is highly conserved and there is a small physicochemical difference between glutamine and arginine. - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Jun 10, 2015 | The Q4429R variant has not been published as pathogenic, nor has it been reported as a benign polymorphism to our knowledge. It was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The Q4429R variant is a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some properties. This substitution occurs at a position that is conserved across species. However, in silico analysis is inconsistent in its predictions as to whether or not the Q4429R variant is damaging to the protein structure/function. Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic or a rare benign variant. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at