chr14-73654877-G-A
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_031427.4(DNAL1):c.34G>A(p.Ala12Thr) variant causes a missense change. The variant allele was found at a frequency of 0.0000546 in 1,539,322 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A12V) has been classified as Uncertain significance.
Frequency
Consequence
NM_031427.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DNAL1 | NM_031427.4 | c.34G>A | p.Ala12Thr | missense_variant | 2/8 | ENST00000553645.7 | |
DNAL1 | NM_001201366.2 | c.-84G>A | 5_prime_UTR_variant | 3/9 | |||
DNAL1 | XM_017021679.3 | c.-84G>A | 5_prime_UTR_variant | 3/9 | |||
DNAL1 | XM_024449715.2 | c.-84G>A | 5_prime_UTR_variant | 3/9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DNAL1 | ENST00000553645.7 | c.34G>A | p.Ala12Thr | missense_variant | 2/8 | 1 | NM_031427.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000133 AC: 2AN: 150564Hom.: 0 Cov.: 31
GnomAD3 exomes AF: 0.0000268 AC: 4AN: 149240Hom.: 0 AF XY: 0.0000381 AC XY: 3AN XY: 78710
GnomAD4 exome AF: 0.0000590 AC: 82AN: 1388758Hom.: 0 Cov.: 33 AF XY: 0.0000540 AC XY: 37AN XY: 684636
GnomAD4 genome ? AF: 0.0000133 AC: 2AN: 150564Hom.: 0 Cov.: 31 AF XY: 0.0000136 AC XY: 1AN XY: 73308
ClinVar
Submissions by phenotype
Primary ciliary dyskinesia 16 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Aug 13, 2022 | This sequence change replaces alanine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 12 of the DNAL1 protein (p.Ala12Thr). This variant is present in population databases (rs763932147, gnomAD 0.007%). This variant has not been reported in the literature in individuals affected with DNAL1-related conditions. ClinVar contains an entry for this variant (Variation ID: 940642). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0"). 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. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at