rs774964160
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_031427.4(DNAL1):āc.81G>Cā(p.Glu27Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000212 in 1,602,424 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_031427.4 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 |
---|---|---|---|---|---|---|---|
DNAL1 | NM_031427.4 | c.81G>C | p.Glu27Asp | missense_variant | 3/8 | ENST00000553645.7 | |
DNAL1 | NM_001201366.2 | c.-37G>C | 5_prime_UTR_variant | 4/9 | |||
DNAL1 | XM_017021679.3 | c.-37G>C | 5_prime_UTR_variant | 4/9 | |||
DNAL1 | XM_024449715.2 | c.-37G>C | 5_prime_UTR_variant | 4/9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DNAL1 | ENST00000553645.7 | c.81G>C | p.Glu27Asp | missense_variant | 3/8 | 1 | NM_031427.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000263 AC: 4AN: 152202Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000987 AC: 24AN: 243178Hom.: 0 AF XY: 0.0000833 AC XY: 11AN XY: 132074
GnomAD4 exome AF: 0.0000207 AC: 30AN: 1450222Hom.: 0 Cov.: 30 AF XY: 0.0000180 AC XY: 13AN XY: 721280
GnomAD4 genome ? AF: 0.0000263 AC: 4AN: 152202Hom.: 0 Cov.: 33 AF XY: 0.0000269 AC XY: 2AN XY: 74366
ClinVar
Submissions by phenotype
Primary ciliary dyskinesia 16 Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | May 02, 2022 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Oct 24, 2022 | This sequence change replaces glutamic acid, which is acidic and polar, with aspartic acid, which is acidic and polar, at codon 27 of the DNAL1 protein (p.Glu27Asp). This variant is present in population databases (rs774964160, gnomAD 0.07%). 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: 220484). 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. - |
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jan 19, 2022 | The c.81G>C (p.E27D) alteration is located in exon 3 (coding exon 3) of the DNAL1 gene. This alteration results from a G to C substitution at nucleotide position 81, causing the glutamic acid (E) at amino acid position 27 to be replaced by an aspartic acid (D). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at