rs760843520
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4
The NM_001206927.2(DNAH8):c.12244A>G(p.Ile4082Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000387 in 1,550,006 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
NM_001206927.2 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 rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
DNAH8 | NM_001206927.2 | c.12244A>G | p.Ile4082Val | missense_variant | Exon 81 of 93 | ENST00000327475.11 | NP_001193856.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
DNAH8 | ENST00000327475.11 | c.12244A>G | p.Ile4082Val | missense_variant | Exon 81 of 93 | 5 | NM_001206927.2 | ENSP00000333363.7 | ||
DNAH8 | ENST00000359357.7 | c.11593A>G | p.Ile3865Val | missense_variant | Exon 79 of 91 | 2 | ENSP00000352312.3 | |||
DNAH8 | ENST00000449981.6 | c.12244A>G | p.Ile4082Val | missense_variant | Exon 80 of 82 | 5 | ENSP00000415331.2 | |||
DNAH8-AS1 | ENST00000416948.1 | n.52+3482T>C | intron_variant | Intron 1 of 3 | 2 |
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152234Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00000398 AC: 1AN: 250952Hom.: 0 AF XY: 0.00000737 AC XY: 1AN XY: 135620
GnomAD4 exome AF: 0.00000358 AC: 5AN: 1397772Hom.: 0 Cov.: 23 AF XY: 0.00000572 AC XY: 4AN XY: 699444
GnomAD4 genome AF: 0.00000657 AC: 1AN: 152234Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74376
ClinVar
Submissions by phenotype
Primary ciliary dyskinesia Uncertain:1
This variant is present in population databases (rs760843520, ExAC 0.01%). 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. 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 and their clinical significance is uncertain. This variant has not been reported in the literature in individuals with DNAH8-related conditions. ClinVar contains an entry for this variant (Variation ID: 407290). This sequence change replaces isoleucine with valine at codon 4082 of the DNAH8 protein (p.Ile4082Val). The isoleucine residue is highly conserved and there is a small physicochemical difference between isoleucine and valine. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at