rs796052095
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP5_Moderate
The NM_145207.3(SPATA5):c.556C>T(p.Arg186Ter) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000093 in 1,613,662 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (★). Variant results in nonsense mediated mRNA decay.
Frequency
Consequence
NM_145207.3 stop_gained
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SPATA5 | NM_145207.3 | c.556C>T | p.Arg186Ter | stop_gained | 5/16 | ENST00000274008.5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
AFG2A | ENST00000274008.5 | c.556C>T | p.Arg186Ter | stop_gained | 5/16 | 1 | NM_145207.3 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000132 AC: 2AN: 152076Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.00000797 AC: 2AN: 251016Hom.: 0 AF XY: 0.0000147 AC XY: 2AN XY: 135650
GnomAD4 exome AF: 0.00000889 AC: 13AN: 1461586Hom.: 0 Cov.: 31 AF XY: 0.0000110 AC XY: 8AN XY: 727056
GnomAD4 genome ? AF: 0.0000132 AC: 2AN: 152076Hom.: 0 Cov.: 33 AF XY: 0.0000269 AC XY: 2AN XY: 74272
ClinVar
Submissions by phenotype
Microcephaly-intellectual disability-sensorineural hearing loss-epilepsy-abnormal muscle tone syndrome Pathogenic:2
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Aug 16, 2022 | This sequence change creates a premature translational stop signal (p.Arg186*) in the SPATA5 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in SPATA5 are known to be pathogenic (PMID: 26299366). This variant is present in population databases (rs796052095, gnomAD 0.003%). This premature translational stop signal has been observed in individuals with syndromic epilepsy (PMID: 26299366). ClinVar contains an entry for this variant (Variation ID: 204306). For these reasons, this variant has been classified as Pathogenic. - |
Pathogenic, no assertion criteria provided | literature only | OMIM | Sep 03, 2015 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at