rs139089747
Variant summary
Our verdict is Benign. Variant got -11 ACMG points: 2P and 13B. PM2BP4_StrongBP6_Very_StrongBP7
The NM_145207.3(SPATA5):c.1131G>A(p.Glu377=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00017 in 1,578,160 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.0010 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000081 ( 0 hom. )
Consequence
SPATA5
NM_145207.3 synonymous
NM_145207.3 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.712
Genes affected
AFG2A (HGNC:18119): (AFG2 AAA ATPase homolog A) This gene encodes a member of the ATPase associated with diverse activities family, whose members are defined by a highly conserved ATPase domain. Members of this family participate in diverse cellular processes that include membrane fusion, DNA replication, microtubule severing, and protein degradation. The protein encoded by this gene has a putative mitochondrial targeting sequence and has been proposed to function in maintenance of mitochondrial function and integrity during mouse spermatogenesis. Allelic variants in this gene have been associated with epilepsy, hearing loss, and cognitive disability syndrome. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Sep 2016]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -11 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.8).
BP6
?
Variant 4-122934722-G-A is Benign according to our data. Variant chr4-122934722-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 475715.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
Synonymous conserved (PhyloP=0.712 with no splicing effect.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SPATA5 | NM_145207.3 | c.1131G>A | p.Glu377= | synonymous_variant | 5/16 | ENST00000274008.5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
AFG2A | ENST00000274008.5 | c.1131G>A | p.Glu377= | synonymous_variant | 5/16 | 1 | NM_145207.3 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00101 AC: 153AN: 152180Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.000282 AC: 60AN: 212786Hom.: 0 AF XY: 0.000236 AC XY: 27AN XY: 114570
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GnomAD4 exome AF: 0.0000807 AC: 115AN: 1425862Hom.: 0 Cov.: 31 AF XY: 0.0000650 AC XY: 46AN XY: 707164
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:5
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:3
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Mar 01, 2023 | AFG2A: BP4, BP7 - |
Benign, criteria provided, single submitter | clinical testing | Athena Diagnostics | Jan 16, 2019 | - - |
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Oct 03, 2019 | - - |
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | May 21, 2019 | - - |
Microcephaly-intellectual disability-sensorineural hearing loss-epilepsy-abnormal muscle tone syndrome Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Oct 04, 2022 | - - |
Computational scores
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Name
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BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at