rs141873943
Variant summary
Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2
The NM_031427.4(DNAL1):āc.415C>Gā(p.Leu139Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00269 in 1,553,030 control chromosomes in the GnomAD database, including 9 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_031427.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -9 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DNAL1 | NM_031427.4 | c.415C>G | p.Leu139Val | missense_variant | 7/8 | ENST00000553645.7 | |
DNAL1 | NM_001201366.2 | c.298C>G | p.Leu100Val | missense_variant | 8/9 | ||
DNAL1 | XM_017021679.3 | c.298C>G | p.Leu100Val | missense_variant | 8/9 | ||
DNAL1 | XM_024449715.2 | c.298C>G | p.Leu100Val | missense_variant | 8/9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DNAL1 | ENST00000553645.7 | c.415C>G | p.Leu139Val | missense_variant | 7/8 | 1 | NM_031427.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00195 AC: 296AN: 152170Hom.: 0 Cov.: 30
GnomAD3 exomes AF: 0.00170 AC: 272AN: 160362Hom.: 0 AF XY: 0.00167 AC XY: 141AN XY: 84302
GnomAD4 exome AF: 0.00277 AC: 3876AN: 1400742Hom.: 9 Cov.: 31 AF XY: 0.00261 AC XY: 1805AN XY: 690976
GnomAD4 genome ? AF: 0.00194 AC: 296AN: 152288Hom.: 0 Cov.: 30 AF XY: 0.00187 AC XY: 139AN XY: 74456
ClinVar
Submissions by phenotype
Primary ciliary dyskinesia 16 Uncertain:1Benign:1
Uncertain significance, criteria provided, single submitter | clinical testing | ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories | Oct 06, 2023 | The DNAL1 c.415C>G; p.Leu139Val variant (rs141873943; ClinVar Variation ID: 178765) has been observed in a cohort of patients referred for Bronchiectasis, but no additional evidence of causality was provided (Olm 2019). This variant is found in the Latino population with an allele frequency of 0.34% (88/25652 alleles) in the Genome Aggregation Database. The leucine at codon 139 is highly conserved, but computational analyses are uncertain whether this variant is neutral or deleterious (REVEL: 0.241). Due to limited information, the clinical significance of the p.Leu139Val variant is uncertain at this time. References: Olm MAK et al. Severe pulmonary disease in an adult primary ciliary dyskinesia population in Brazil. Sci Rep. 2019 Jun 18;9(1):8693. PMID: 31213628 - |
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 23, 2024 | - - |
not specified Benign:2
Likely benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Feb 21, 2013 | Leu100Val in exon 8 of DNAL1: This variant is not expected to have clinical sign ificance because it has been identified in 0.4% (30/8054) of European American c hromosomes from a broad population by the NHLBI Exome Sequencing Project (http:/ /evs.gs.washington.edu/EVS; dbSNP rs141873943). - |
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Sep 05, 2014 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at