rs878855237
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_003114.5(SPAG1):āc.1360G>Cā(p.Glu454Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000185 in 1,423,540 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_003114.5 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 | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
SPAG1 | NM_003114.5 | c.1360G>C | p.Glu454Gln | missense_variant | 11/19 | ENST00000388798.7 | NP_003105.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
SPAG1 | ENST00000388798.7 | c.1360G>C | p.Glu454Gln | missense_variant | 11/19 | 1 | NM_003114.5 | ENSP00000373450.3 | ||
SPAG1 | ENST00000251809.4 | c.1360G>C | p.Glu454Gln | missense_variant | 11/19 | 5 | ENSP00000251809.3 | |||
SPAG1 | ENST00000523302.1 | n.267G>C | non_coding_transcript_exon_variant | 1/3 | 3 |
Frequencies
GnomAD3 genomes AF: 0.000171 AC: 26AN: 151874Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000774 AC: 5AN: 64606Hom.: 0 AF XY: 0.0000800 AC XY: 3AN XY: 37494
GnomAD4 exome AF: 0.000187 AC: 238AN: 1271666Hom.: 0 Cov.: 32 AF XY: 0.000162 AC XY: 101AN XY: 625168
GnomAD4 genome AF: 0.000171 AC: 26AN: 151874Hom.: 0 Cov.: 33 AF XY: 0.000121 AC XY: 9AN XY: 74190
ClinVar
Submissions by phenotype
Primary ciliary dyskinesia 28 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jan 16, 2024 | This sequence change replaces glutamic acid, which is acidic and polar, with glutamine, which is neutral and polar, at codon 454 of the SPAG1 protein (p.Glu454Gln). This variant is present in population databases (no rsID available, gnomAD 0.02%). This variant has not been reported in the literature in individuals affected with SPAG1-related conditions. ClinVar contains an entry for this variant (Variation ID: 242011). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt SPAG1 protein function with a negative predictive value of 80%. 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 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Aug 22, 2021 | The p.E454Q variant (also known as c.1360G>C), located in coding exon 10 of the SPAG1 gene, results from a G to C substitution at nucleotide position 1360. The glutamic acid at codon 454 is replaced by glutamine, an amino acid with highly similar properties. This amino acid position is conserved. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at