rs761136963
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2
The NM_178452.6(DNAAF1):c.1377T>A(p.Asp459Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000217 in 1,611,238 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D459A) has been classified as Uncertain significance.
Frequency
Consequence
NM_178452.6 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Benign. Variant got -20 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DNAAF1 | NM_178452.6 | c.1377T>A | p.Asp459Glu | missense_variant | 8/12 | ENST00000378553.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DNAAF1 | ENST00000378553.10 | c.1377T>A | p.Asp459Glu | missense_variant | 8/12 | 1 | NM_178452.6 | P1 | |
DNAAF1 | ENST00000563818.5 | n.1054T>A | non_coding_transcript_exon_variant | 4/8 | 2 | ||||
DNAAF1 | ENST00000570298.5 | n.1531T>A | non_coding_transcript_exon_variant | 8/11 | 2 | ||||
DNAAF1 | ENST00000563093.5 | c.1226-37T>A | intron_variant, NMD_transcript_variant | 2 |
Frequencies
GnomAD3 genomes AF: 0.000139 AC: 21AN: 150900Hom.: 0 Cov.: 31
GnomAD3 exomes AF: 0.00115 AC: 288AN: 251116Hom.: 3 AF XY: 0.000781 AC XY: 106AN XY: 135804
GnomAD4 exome AF: 0.000225 AC: 328AN: 1460222Hom.: 4 Cov.: 94 AF XY: 0.000169 AC XY: 123AN XY: 726454
GnomAD4 genome AF: 0.000139 AC: 21AN: 151016Hom.: 0 Cov.: 31 AF XY: 0.000136 AC XY: 10AN XY: 73772
ClinVar
Submissions by phenotype
Primary ciliary dyskinesia Benign:2
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Jun 21, 2016 | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 05, 2024 | - - |
Primary ciliary dyskinesia 13 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Feb 25, 2022 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at