chr8-100162385-T-G
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4
The NM_003114.5(SPAG1):c.105T>G(p.Asp35Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000693 in 1,588,220 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign 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. D35N) 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 1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SPAG1 | NM_003114.5 | c.105T>G | p.Asp35Glu | missense_variant | 2/19 | ENST00000388798.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SPAG1 | ENST00000388798.7 | c.105T>G | p.Asp35Glu | missense_variant | 2/19 | 1 | NM_003114.5 | P1 | |
SPAG1 | ENST00000251809.4 | c.105T>G | p.Asp35Glu | missense_variant | 2/19 | 5 | P1 | ||
SPAG1 | ENST00000520508.5 | c.105T>G | p.Asp35Glu | missense_variant | 2/10 | 5 | |||
SPAG1 | ENST00000520643.5 | c.105T>G | p.Asp35Glu | missense_variant | 2/10 | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.0000197 AC: 3AN: 152204Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000269 AC: 6AN: 223404Hom.: 1 AF XY: 0.0000248 AC XY: 3AN XY: 120868
GnomAD4 exome AF: 0.00000557 AC: 8AN: 1436016Hom.: 1 Cov.: 28 AF XY: 0.00000560 AC XY: 4AN XY: 713828
GnomAD4 genome ? AF: 0.0000197 AC: 3AN: 152204Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74358
ClinVar
Submissions by phenotype
Primary ciliary dyskinesia 28 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Aug 09, 2022 | This sequence change replaces aspartic acid, which is acidic and polar, with glutamic acid, which is acidic and polar, at codon 35 of the SPAG1 protein (p.Asp35Glu). This variant is present in population databases (no rsID available, gnomAD 0.02%), including at least one homozygous and/or hemizygous individual. 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: 658911). 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