rs777488014
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_003114.5(SPAG1):c.977C>T(p.Ser326Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000188 in 1,591,958 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar 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 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SPAG1 | NM_003114.5 | c.977C>T | p.Ser326Phe | missense_variant | 10/19 | ENST00000388798.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SPAG1 | ENST00000388798.7 | c.977C>T | p.Ser326Phe | missense_variant | 10/19 | 1 | NM_003114.5 | P1 | |
SPAG1 | ENST00000251809.4 | c.977C>T | p.Ser326Phe | missense_variant | 10/19 | 5 | P1 | ||
SPAG1 | ENST00000520508.5 | c.977C>T | p.Ser326Phe | missense_variant | 10/10 | 5 | |||
SPAG1 | ENST00000520643.5 | c.977C>T | p.Ser326Phe | missense_variant | 10/10 | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.0000132 AC: 2AN: 152082Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000170 AC: 4AN: 235680Hom.: 0 AF XY: 0.0000157 AC XY: 2AN XY: 127374
GnomAD4 exome AF: 0.0000194 AC: 28AN: 1439876Hom.: 0 Cov.: 29 AF XY: 0.0000168 AC XY: 12AN XY: 715328
GnomAD4 genome ? AF: 0.0000132 AC: 2AN: 152082Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0AN XY: 74296
ClinVar
Submissions by phenotype
Primary ciliary dyskinesia 28 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Sep 04, 2021 | 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. 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. This variant has not been reported in the literature in individuals affected with SPAG1-related conditions. This variant is present in population databases (rs777488014, ExAC 0.002%). This sequence change replaces serine with phenylalanine at codon 326 of the SPAG1 protein (p.Ser326Phe). The serine residue is weakly conserved and there is a large physicochemical difference between serine and phenylalanine. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at