rs556774863
Variant summary
Our verdict is Benign. Variant got -14 ACMG points: 2P and 16B. PM2BP4_StrongBP6_Very_StrongBS1
The NM_003114.5(SPAG1):āc.1057A>Gā(p.Lys353Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000122 in 1,603,546 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (ā ā ).
Frequency
Consequence
NM_003114.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -14 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
SPAG1 | ENST00000388798.7 | c.1057A>G | p.Lys353Glu | missense_variant | 10/19 | 1 | NM_003114.5 | ENSP00000373450.3 | ||
SPAG1 | ENST00000251809.4 | c.1057A>G | p.Lys353Glu | missense_variant | 10/19 | 5 | ENSP00000251809.3 | |||
SPAG1 | ENST00000520508.5 | c.1057A>G | p.Lys353Glu | missense_variant | 10/10 | 5 | ENSP00000428070.1 | |||
SPAG1 | ENST00000520643.5 | c.1057A>G | p.Lys353Glu | missense_variant | 10/10 | 2 | ENSP00000427716.1 |
Frequencies
GnomAD3 genomes AF: 0.000303 AC: 44AN: 145362Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.000457 AC: 108AN: 236510Hom.: 1 AF XY: 0.000430 AC XY: 55AN XY: 127902
GnomAD4 exome AF: 0.000104 AC: 152AN: 1458056Hom.: 1 Cov.: 30 AF XY: 0.0000868 AC XY: 63AN XY: 725504
GnomAD4 genome AF: 0.000296 AC: 43AN: 145490Hom.: 0 Cov.: 33 AF XY: 0.000324 AC XY: 23AN XY: 70926
ClinVar
Submissions by phenotype
Primary ciliary dyskinesia 28 Benign:2
Likely benign, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | May 03, 2022 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Nov 03, 2023 | - - |
Primary ciliary dyskinesia Benign:1
Benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Jun 22, 2018 | This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
SPAG1-related disorder Benign:1
Likely benign, no assertion criteria provided | clinical testing | PreventionGenetics, part of Exact Sciences | Jun 18, 2019 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at