rs900496106
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_017802.4(DNAAF5):c.502C>G(p.Leu168Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000214 in 1,347,788 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_017802.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DNAAF5 | NM_017802.4 | c.502C>G | p.Leu168Val | missense_variant | 1/13 | ENST00000297440.11 | |
PRKAR1B | NM_001164760.2 | c.-35G>C | 5_prime_UTR_variant | 1/11 | ENST00000537384.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DNAAF5 | ENST00000297440.11 | c.502C>G | p.Leu168Val | missense_variant | 1/13 | 1 | NM_017802.4 | P1 | |
PRKAR1B | ENST00000537384.6 | c.-35G>C | 5_prime_UTR_variant | 1/11 | 5 | NM_001164760.2 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000929 AC: 14AN: 150630Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000533 AC: 2AN: 37540Hom.: 0 AF XY: 0.0000878 AC XY: 2AN XY: 22790
GnomAD4 exome AF: 0.000230 AC: 275AN: 1197048Hom.: 0 Cov.: 31 AF XY: 0.000223 AC XY: 131AN XY: 586338
GnomAD4 genome ? AF: 0.0000929 AC: 14AN: 150740Hom.: 0 Cov.: 32 AF XY: 0.000122 AC XY: 9AN XY: 73590
ClinVar
Submissions by phenotype
Primary ciliary dyskinesia Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jun 03, 2022 | This sequence change replaces leucine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 168 of the DNAAF5 protein (p.Leu168Val). This variant is present in population databases (no rsID available, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with DNAAF5-related conditions. ClinVar contains an entry for this variant (Variation ID: 567179). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The valine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. 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. - |
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Apr 21, 2020 | The p.L168V variant (also known as c.502C>G), located in coding exon 1 of the DNAAF5 gene, results from a C to G substitution at nucleotide position 502. The leucine at codon 168 is replaced by valine, an amino acid with highly similar properties. This amino acid position is poorly conserved in available vertebrate species, and valine is the reference amino acid in other vertebrate species. 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. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at