6-39030126-C-T
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3
The NM_001206927.2(DNAH8):c.13858C>T(p.Leu4620Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000122 in 1,613,780 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. L4620H) has been classified 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 3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DNAH8 | NM_001206927.2 | c.13858C>T | p.Leu4620Phe | missense_variant | 93/93 | ENST00000327475.11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DNAH8 | ENST00000327475.11 | c.13858C>T | p.Leu4620Phe | missense_variant | 93/93 | 5 | NM_001206927.2 | P2 | |
DNAH8 | ENST00000359357.7 | c.13207C>T | p.Leu4403Phe | missense_variant | 91/91 | 2 | A2 |
Frequencies
GnomAD3 genomes AF: 0.000171 AC: 26AN: 152062Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000962 AC: 24AN: 249470Hom.: 0 AF XY: 0.0000742 AC XY: 10AN XY: 134840
GnomAD4 exome AF: 0.000117 AC: 171AN: 1461600Hom.: 0 Cov.: 31 AF XY: 0.000125 AC XY: 91AN XY: 727106
GnomAD4 genome AF: 0.000171 AC: 26AN: 152180Hom.: 0 Cov.: 32 AF XY: 0.000108 AC XY: 8AN XY: 74388
ClinVar
Submissions by phenotype
Primary ciliary dyskinesia Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jun 27, 2022 | This sequence change replaces leucine, which is neutral and non-polar, with phenylalanine, which is neutral and non-polar, at codon 4620 of the DNAH8 protein (p.Leu4620Phe). This variant is present in population databases (rs139810428, gnomAD 0.02%). This variant has not been reported in the literature in individuals affected with DNAH8-related conditions. ClinVar contains an entry for this variant (Variation ID: 407293). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Not Available"; Align-GVGD: "Class C0"). 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