rs780016631
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate
The NM_017802.4(DNAAF5):c.676G>C(p.Ala226Pro) variant causes a missense change. The variant allele was found at a frequency of 0.00000372 in 1,614,010 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 (★). Synonymous variant affecting the same amino acid position (i.e. A226A) has been classified as Likely benign.
Frequency
Consequence
NM_017802.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DNAAF5 | NM_017802.4 | c.676G>C | p.Ala226Pro | missense_variant | 2/13 | ENST00000297440.11 | |
DNAAF5 | XM_024446813.2 | c.676G>C | p.Ala226Pro | missense_variant | 2/12 | ||
DNAAF5 | NR_075098.2 | n.636G>C | non_coding_transcript_exon_variant | 2/13 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DNAAF5 | ENST00000297440.11 | c.676G>C | p.Ala226Pro | missense_variant | 2/13 | 1 | NM_017802.4 | P1 | |
DNAAF5 | ENST00000440747.5 | c.82G>C | p.Ala28Pro | missense_variant | 2/13 | 2 | |||
DNAAF5 | ENST00000437419.5 | c.97+2428G>C | intron_variant | 5 | |||||
DNAAF5 | ENST00000438961.1 | n.145G>C | non_coding_transcript_exon_variant | 2/5 | 4 |
Frequencies
GnomAD3 genomes ? AF: 0.0000131 AC: 2AN: 152202Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00000399 AC: 1AN: 250696Hom.: 0 AF XY: 0.00000737 AC XY: 1AN XY: 135738
GnomAD4 exome AF: 0.00000274 AC: 4AN: 1461808Hom.: 0 Cov.: 31 AF XY: 0.00000275 AC XY: 2AN XY: 727222
GnomAD4 genome ? AF: 0.0000131 AC: 2AN: 152202Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2AN XY: 74354
ClinVar
Submissions by phenotype
Primary ciliary dyskinesia Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Aug 03, 2017 | 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 do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals with DNAAF5-related disease. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the ExAC database. This sequence change replaces alanine with proline at codon 226 of the DNAAF5 protein (p.Ala226Pro). The alanine residue is moderately conserved and there is a small physicochemical difference between alanine and proline. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at