chr4-122979302-G-T
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Variant summary
Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BS1BS2
The NM_145207.3(SPATA5):c.1785G>T(p.Val595=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0114 in 1,614,198 control chromosomes in the GnomAD database, including 158 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.0091 ( 12 hom., cov: 33)
Exomes 𝑓: 0.012 ( 146 hom. )
Consequence
SPATA5
NM_145207.3 synonymous
NM_145207.3 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 2.64
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 -19 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.43).
BP6
Variant 4-122979302-G-T is Benign according to our data. Variant chr4-122979302-G-T is described in ClinVar as [Likely_benign]. Clinvar id is 475723.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=2.64 with no splicing effect.
BS1
Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.00912 (1390/152330) while in subpopulation SAS AF= 0.028 (135/4824). AF 95% confidence interval is 0.0241. There are 12 homozygotes in gnomad4. There are 770 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
BS2
High Homozygotes in GnomAd4 at 12 gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SPATA5 | NM_145207.3 | c.1785G>T | p.Val595= | synonymous_variant | 10/16 | ENST00000274008.5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
AFG2A | ENST00000274008.5 | c.1785G>T | p.Val595= | synonymous_variant | 10/16 | 1 | NM_145207.3 | P1 | |
AFG2A | ENST00000422835.2 | n.1827G>T | non_coding_transcript_exon_variant | 10/15 | 1 | ||||
AFG2A | ENST00000675612.1 | c.1854G>T | p.Val618= | synonymous_variant | 11/17 | ||||
AFG2A | ENST00000674886.1 | n.1847G>T | non_coding_transcript_exon_variant | 10/11 |
Frequencies
GnomAD3 genomes AF: 0.00913 AC: 1389AN: 152212Hom.: 12 Cov.: 33
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GnomAD3 exomes AF: 0.0115 AC: 2891AN: 251472Hom.: 26 AF XY: 0.0131 AC XY: 1785AN XY: 135904
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GnomAD4 exome AF: 0.0117 AC: 17062AN: 1461868Hom.: 146 Cov.: 30 AF XY: 0.0123 AC XY: 8932AN XY: 727230
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GnomAD4 genome AF: 0.00912 AC: 1390AN: 152330Hom.: 12 Cov.: 33 AF XY: 0.0103 AC XY: 770AN XY: 74494
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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:2
Benign, criteria provided, single submitter | clinical testing | Athena Diagnostics | Feb 09, 2018 | - - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Aug 17, 2021 | - - |
Microcephaly-intellectual disability-sensorineural hearing loss-epilepsy-abnormal muscle tone syndrome Benign:2
Likely benign, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Jul 19, 2021 | - - |
Benign, criteria provided, single submitter | clinical testing | Invitae | Nov 03, 2022 | - - |
AFG2A-related disorder Benign:1
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Aug 07, 2019 | This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at