rs971341609
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_003114.5(SPAG1):āc.1229C>Gā(p.Pro410Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000718 in 1,393,010 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 Uncertain significance (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.1229C>G | p.Pro410Arg | 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.1229C>G | p.Pro410Arg | missense_variant | 11/19 | 1 | NM_003114.5 | ENSP00000373450.3 | ||
SPAG1 | ENST00000251809.4 | c.1229C>G | p.Pro410Arg | missense_variant | 11/19 | 5 | ENSP00000251809.3 | |||
SPAG1 | ENST00000523302.1 | n.136C>G | non_coding_transcript_exon_variant | 1/3 | 3 |
Frequencies
GnomAD3 genomes AF: 0.0000399 AC: 6AN: 150332Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000425 AC: 2AN: 47022Hom.: 0 AF XY: 0.0000699 AC XY: 2AN XY: 28626
GnomAD4 exome AF: 0.00000322 AC: 4AN: 1242678Hom.: 0 Cov.: 32 AF XY: 0.00000327 AC XY: 2AN XY: 612122
GnomAD4 genome AF: 0.0000399 AC: 6AN: 150332Hom.: 0 Cov.: 33 AF XY: 0.0000272 AC XY: 2AN XY: 73402
ClinVar
Submissions by phenotype
Primary ciliary dyskinesia 28 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Feb 28, 2022 | This sequence change replaces proline, which is neutral and non-polar, with arginine, which is basic and polar, at codon 410 of the SPAG1 protein (p.Pro410Arg). This variant is present in population databases (no rsID available, gnomAD 0.03%). 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: 410991). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. 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