8-100162369-T-C
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3
The NM_003114.5(SPAG1):c.89T>C(p.Ile30Thr) variant causes a missense change. The variant allele was found at a frequency of 0.00000188 in 1,596,710 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. I30V) has been classified as Uncertain significance.
Frequency
Consequence
NM_003114.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 3 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
SPAG1 | ENST00000388798.7 | c.89T>C | p.Ile30Thr | missense_variant | Exon 2 of 19 | 1 | NM_003114.5 | ENSP00000373450.3 | ||
SPAG1 | ENST00000251809.4 | c.89T>C | p.Ile30Thr | missense_variant | Exon 2 of 19 | 5 | ENSP00000251809.3 | |||
SPAG1 | ENST00000520508.5 | c.89T>C | p.Ile30Thr | missense_variant | Exon 2 of 10 | 5 | ENSP00000428070.1 | |||
SPAG1 | ENST00000520643.5 | c.89T>C | p.Ile30Thr | missense_variant | Exon 2 of 10 | 2 | ENSP00000427716.1 |
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152218Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.00000431 AC: 1AN: 232204Hom.: 0 AF XY: 0.00000798 AC XY: 1AN XY: 125276
GnomAD4 exome AF: 0.00000138 AC: 2AN: 1444492Hom.: 0 Cov.: 28 AF XY: 0.00000279 AC XY: 2AN XY: 717960
GnomAD4 genome AF: 0.00000657 AC: 1AN: 152218Hom.: 0 Cov.: 33 AF XY: 0.0000134 AC XY: 1AN XY: 74352
ClinVar
Submissions by phenotype
Primary ciliary dyskinesia 28 Uncertain:1
This variant is not present in population databases (ExAC no frequency). This sequence change replaces isoleucine with threonine at codon 30 of the SPAG1 protein (p.Ile30Thr). The isoleucine residue is moderately conserved and there is a moderate physicochemical difference between isoleucine and threonine. This variant has not been reported in the literature in individuals with SPAG1-related conditions. 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: "Probably Damaging"; 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. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at