rs878854968
Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_012144.4(DNAI1):āc.912C>Gā(p.Tyr304Ter) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000186 in 1,613,240 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 Pathogenic (ā ). Variant results in nonsense mediated mRNA decay.
Frequency
Consequence
NM_012144.4 stop_gained
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 12 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DNAI1 | NM_012144.4 | c.912C>G | p.Tyr304Ter | stop_gained | 11/20 | ENST00000242317.9 | |
DNAI1 | NM_001281428.2 | c.924C>G | p.Tyr308Ter | stop_gained | 11/20 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DNAI1 | ENST00000242317.9 | c.912C>G | p.Tyr304Ter | stop_gained | 11/20 | 1 | NM_012144.4 | ||
DNAI1 | ENST00000614641.4 | c.924C>G | p.Tyr308Ter | stop_gained | 11/20 | 5 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00000657 AC: 1AN: 152146Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00000399 AC: 1AN: 250864Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135576
GnomAD4 exome AF: 0.00000137 AC: 2AN: 1461094Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1AN XY: 726834
GnomAD4 genome ? AF: 0.00000657 AC: 1AN: 152146Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74314
ClinVar
Submissions by phenotype
Primary ciliary dyskinesia Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Feb 15, 2016 | For these reasons, this variant has been classified as Pathogenic. While this particular variant has not been reported in the literature, truncating variants in DNAI1 are known to be pathogenic (PMID: 16858015). This sequence change creates a premature translational stop signal at codon 304 (p.Tyr304*) of the DNAI1 gene. It is expected to result in an absent or disrupted protein product. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at