rs201109134
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 3P and 3B. PM2PP2BP4_ModerateBP6
The NM_001376.5(DYNC1H1):āc.10473A>Cā(p.Lys3491Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,806 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Synonymous variant affecting the same amino acid position (i.e. K3491K) has been classified as Likely benign.
Frequency
Consequence
NM_001376.5 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DYNC1H1 | NM_001376.5 | c.10473A>C | p.Lys3491Asn | missense_variant | 55/78 | ENST00000360184.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DYNC1H1 | ENST00000360184.10 | c.10473A>C | p.Lys3491Asn | missense_variant | 55/78 | 1 | NM_001376.5 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251360Hom.: 0 AF XY: 0.00000736 AC XY: 1AN XY: 135884
GnomAD4 exome AF: 0.00000137 AC: 2AN: 1461806Hom.: 0 Cov.: 31 AF XY: 0.00000275 AC XY: 2AN XY: 727182
GnomAD4 genome ? Cov.: 32
ClinVar
Submissions by phenotype
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jan 30, 2022 | The p.K3491N variant (also known as c.10473A>C), located in coding exon 55 of the DYNC1H1 gene, results from an A to C substitution at nucleotide position 10473. The lysine at codon 3491 is replaced by asparagine, an amino acid with similar properties. This amino acid position is conserved. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. - |
DYNC1H1-related disorder Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Sep 19, 2022 | The DYNC1H1 c.10473A>C variant is predicted to result in the amino acid substitution p.Lys3491Asn. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.0029% of alleles in individuals of Latino descent in gnomAD (http://gnomad.broadinstitute.org/variant/14-102500372-A-C). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. - |
Charcot-Marie-Tooth disease axonal type 2O Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jun 23, 2023 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at