rs150058325
Positions:
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_145207.3(SPATA5):c.367G>T(p.Val123Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00007 in 1,613,596 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 Uncertain significance (★★).
Frequency
Genomes: 𝑓 0.00039 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000036 ( 0 hom. )
Consequence
SPATA5
NM_145207.3 missense
NM_145207.3 missense
Scores
6
12
Clinical Significance
Conservation
PhyloP100: 6.37
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 Likely_benign. Variant got -2 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (MetaRNN=0.018812716).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SPATA5 | NM_145207.3 | c.367G>T | p.Val123Leu | missense_variant | 3/16 | ENST00000274008.5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
AFG2A | ENST00000274008.5 | c.367G>T | p.Val123Leu | missense_variant | 3/16 | 1 | NM_145207.3 | P1 | |
AFG2A | ENST00000422835.2 | n.409G>T | non_coding_transcript_exon_variant | 3/15 | 1 | ||||
AFG2A | ENST00000675612.1 | c.364G>T | p.Val122Leu | missense_variant | 3/17 | ||||
AFG2A | ENST00000674886.1 | n.429G>T | non_coding_transcript_exon_variant | 3/11 |
Frequencies
GnomAD3 genomes ? AF: 0.000394 AC: 60AN: 152202Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000918 AC: 23AN: 250498Hom.: 0 AF XY: 0.0000960 AC XY: 13AN XY: 135436
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GnomAD4 exome AF: 0.0000363 AC: 53AN: 1461276Hom.: 0 Cov.: 30 AF XY: 0.0000358 AC XY: 26AN XY: 726942
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GnomAD4 genome ? AF: 0.000394 AC: 60AN: 152320Hom.: 0 Cov.: 32 AF XY: 0.000416 AC XY: 31AN XY: 74484
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Aug 09, 2022 | In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge - |
Microcephaly-intellectual disability-sensorineural hearing loss-epilepsy-abnormal muscle tone syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Sep 01, 2022 | This sequence change replaces valine, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 123 of the SPATA5 protein (p.Val123Leu). This variant is present in population databases (rs150058325, gnomAD 0.2%). This variant has not been reported in the literature in individuals affected with SPATA5-related conditions. ClinVar contains an entry for this variant (Variation ID: 475729). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C25"). 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. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Uncertain
DEOGEN2
Benign
T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
T
M_CAP
Benign
D
MetaRNN
Benign
T
MetaSVM
Uncertain
T
MutationTaster
Benign
D
PrimateAI
Uncertain
T
PROVEAN
Benign
N
REVEL
Uncertain
Sift
Benign
T
Sift4G
Benign
T
Polyphen
B
Vest4
MutPred
Gain of loop (P = 0.0079);
MVP
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ClinPred
T
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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