rs143717300
Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2BP4_StrongBP6
The NM_012472.6(DNAAF11):āc.644A>Gā(p.Asn215Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000352 in 1,608,812 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Synonymous variant affecting the same amino acid position (i.e. N215N) has been classified as Likely benign.
Frequency
Consequence
NM_012472.6 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DNAAF11 | NM_012472.6 | c.644A>G | p.Asn215Ser | missense_variant | 5/12 | ENST00000620350.5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DNAAF11 | ENST00000620350.5 | c.644A>G | p.Asn215Ser | missense_variant | 5/12 | 1 | NM_012472.6 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.000223 AC: 34AN: 152216Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000127 AC: 32AN: 251270Hom.: 0 AF XY: 0.000147 AC XY: 20AN XY: 135824
GnomAD4 exome AF: 0.000366 AC: 533AN: 1456596Hom.: 1 Cov.: 29 AF XY: 0.000338 AC XY: 245AN XY: 725126
GnomAD4 genome ? AF: 0.000223 AC: 34AN: 152216Hom.: 0 Cov.: 32 AF XY: 0.000188 AC XY: 14AN XY: 74368
ClinVar
Submissions by phenotype
Primary ciliary dyskinesia 19 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Aug 23, 2022 | This sequence change replaces asparagine, which is neutral and polar, with serine, which is neutral and polar, at codon 215 of the LRRC6 protein (p.Asn215Ser). This variant is present in population databases (rs143717300, gnomAD 0.03%). This variant has not been reported in the literature in individuals affected with LRRC6-related conditions. ClinVar contains an entry for this variant (Variation ID: 582972). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The serine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. 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. - |
Primary ciliary dyskinesia Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Apr 09, 2022 | 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. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at