rs141605537
Variant summary
Our verdict is Benign. Variant got -7 ACMG points: 2P and 9B. PM2BP4_StrongBP6BS1
The NM_003114.5(SPAG1):āc.413T>Cā(p.Leu138Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000185 in 1,612,570 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 Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_003114.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -7 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SPAG1 | NM_003114.5 | c.413T>C | p.Leu138Pro | missense_variant | 4/19 | ENST00000388798.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SPAG1 | ENST00000388798.7 | c.413T>C | p.Leu138Pro | missense_variant | 4/19 | 1 | NM_003114.5 | P1 | |
SPAG1 | ENST00000251809.4 | c.413T>C | p.Leu138Pro | missense_variant | 4/19 | 5 | P1 | ||
SPAG1 | ENST00000520508.5 | c.413T>C | p.Leu138Pro | missense_variant | 4/10 | 5 | |||
SPAG1 | ENST00000520643.5 | c.413T>C | p.Leu138Pro | missense_variant | 4/10 | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.000841 AC: 128AN: 152218Hom.: 1 Cov.: 32
GnomAD3 exomes AF: 0.000274 AC: 68AN: 248560Hom.: 0 AF XY: 0.000171 AC XY: 23AN XY: 134594
GnomAD4 exome AF: 0.000116 AC: 169AN: 1460234Hom.: 0 Cov.: 28 AF XY: 0.000105 AC XY: 76AN XY: 726480
GnomAD4 genome ? AF: 0.000847 AC: 129AN: 152336Hom.: 1 Cov.: 32 AF XY: 0.000805 AC XY: 60AN XY: 74494
ClinVar
Submissions by phenotype
Primary ciliary dyskinesia 28 Uncertain:1Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 20, 2024 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Baylor Genetics | May 11, 2018 | This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868]. - |
Primary ciliary dyskinesia Benign:1
Benign, criteria provided, single submitter | clinical testing | Ambry Genetics | May 15, 2017 | 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, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Mar 10, 2023 | 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