8-100162368-A-G
Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2BP4_StrongBS1_Supporting
The NM_003114.5(SPAG1):āc.88A>Gā(p.Ile30Val) variant causes a missense change. The variant allele was found at a frequency of 0.0000757 in 1,598,092 control chromosomes in the GnomAD database, including 1 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 Uncertain significance (ā ā ). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. I30T) has been classified as Uncertain significance.
Frequency
Consequence
NM_003114.5 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 |
---|---|---|---|---|---|---|---|
SPAG1 | NM_003114.5 | c.88A>G | p.Ile30Val | missense_variant | 2/19 | ENST00000388798.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SPAG1 | ENST00000388798.7 | c.88A>G | p.Ile30Val | missense_variant | 2/19 | 1 | NM_003114.5 | P1 | |
SPAG1 | ENST00000251809.4 | c.88A>G | p.Ile30Val | missense_variant | 2/19 | 5 | P1 | ||
SPAG1 | ENST00000520508.5 | c.88A>G | p.Ile30Val | missense_variant | 2/10 | 5 | |||
SPAG1 | ENST00000520643.5 | c.88A>G | p.Ile30Val | missense_variant | 2/10 | 2 |
Frequencies
GnomAD3 genomes AF: 0.000184 AC: 28AN: 152246Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.000137 AC: 32AN: 234176Hom.: 0 AF XY: 0.000158 AC XY: 20AN XY: 126312
GnomAD4 exome AF: 0.0000643 AC: 93AN: 1445728Hom.: 1 Cov.: 28 AF XY: 0.0000640 AC XY: 46AN XY: 718748
GnomAD4 genome AF: 0.000184 AC: 28AN: 152364Hom.: 0 Cov.: 33 AF XY: 0.000255 AC XY: 19AN XY: 74512
ClinVar
Submissions by phenotype
Primary ciliary dyskinesia Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Dec 12, 2016 | The p.I30V variant (also known as c.88A>G), located in coding exon 1 of the SPAG1 gene, results from an A to G substitution at nucleotide position 88. The isoleucine at codon 30 is replaced by valine, an amino acid with highly similar properties. This amino acid position is well conserved in available vertebrate species; however, valine is the reference amino acid in other vertebrate species. 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. - |
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jun 22, 2021 | The c.88A>G (p.I30V) alteration is located in exon 2 (coding exon 1) of the SPAG1 gene. This alteration results from a A to G substitution at nucleotide position 88, causing the isoleucine (I) at amino acid position 30 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Primary ciliary dyskinesia 28 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jul 28, 2022 | This sequence change replaces isoleucine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 30 of the SPAG1 protein (p.Ile30Val). This variant is present in population databases (rs550123264, gnomAD 0.1%). This variant has not been reported in the literature in individuals affected with SPAG1-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The valine 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. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at