rs757727188
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_178452.6(DNAAF1):āc.1191G>Cā(p.Glu397Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000013 in 1,461,518 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 Uncertain significance (ā ā ).
Frequency
Consequence
NM_178452.6 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 |
---|---|---|---|---|---|---|---|
DNAAF1 | NM_178452.6 | c.1191G>C | p.Glu397Asp | missense_variant | 8/12 | ENST00000378553.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DNAAF1 | ENST00000378553.10 | c.1191G>C | p.Glu397Asp | missense_variant | 8/12 | 1 | NM_178452.6 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 exomes AF: 0.0000318 AC: 8AN: 251260Hom.: 0 AF XY: 0.0000294 AC XY: 4AN XY: 135826
GnomAD4 exome AF: 0.0000130 AC: 19AN: 1461518Hom.: 0 Cov.: 94 AF XY: 0.00000963 AC XY: 7AN XY: 727066
GnomAD4 genome ? Cov.: 32
ClinVar
Submissions by phenotype
Primary ciliary dyskinesia Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jun 17, 2022 | The c.1191G>C (p.E397D) alteration is located in exon 8 (coding exon 8) of the DNAAF1 gene. This alteration results from a G to C substitution at nucleotide position 1191, causing the glutamic acid (E) at amino acid position 397 to be replaced by an aspartic acid (D). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Aug 01, 2018 | This variant is present in population databases (rs757727188, ExAC 0.006%). 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 DNAAF1-related disease. ClinVar contains an entry for this variant (Variation ID: 216830). This sequence change replaces glutamic acid with aspartic acid at codon 397 of the DNAAF1 protein (p.Glu397Asp). The glutamic acid residue is weakly conserved and there is a small physicochemical difference between glutamic acid and aspartic acid. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at