rs752274594
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Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 2P and 8B. PM2BP6_Very_Strong
The NM_145207.3(AFG2A):c.1334+6_1334+9delCTTT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000721 in 1,594,816 control chromosomes in the GnomAD database, with no homozygous occurrence. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.000033 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000076 ( 0 hom. )
Consequence
AFG2A
NM_145207.3 splice_region, intron
NM_145207.3 splice_region, intron
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 1.34
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 -6 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP6
Variant 4-122936160-CTCTT-C is Benign according to our data. Variant chr4-122936160-CTCTT-C is described in ClinVar as [Likely_benign]. Clinvar id is 475718.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
AFG2A | NM_145207.3 | c.1334+6_1334+9delCTTT | splice_region_variant, intron_variant | ENST00000274008.5 | NP_660208.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
SPATA5 | ENST00000274008.5 | c.1334+6_1334+9delCTTT | splice_region_variant, intron_variant | 1 | NM_145207.3 | ENSP00000274008.3 | ||||
SPATA5 | ENST00000422835.2 | n.1376+6_1376+9delCTTT | splice_region_variant, intron_variant | 1 | ||||||
SPATA5 | ENST00000675612.1 | c.1331+6_1331+9delCTTT | splice_region_variant, intron_variant | ENSP00000502453.1 | ||||||
SPATA5 | ENST00000674886.1 | n.1396+6_1396+9delCTTT | splice_region_variant, intron_variant |
Frequencies
GnomAD3 genomes AF: 0.0000329 AC: 5AN: 152058Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.000422 AC: 102AN: 241730Hom.: 0 AF XY: 0.000337 AC XY: 44AN XY: 130584
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GnomAD4 exome AF: 0.0000762 AC: 110AN: 1442758Hom.: 0 AF XY: 0.0000670 AC XY: 48AN XY: 716950
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GnomAD4 genome AF: 0.0000329 AC: 5AN: 152058Hom.: 0 Cov.: 32 AF XY: 0.0000539 AC XY: 4AN XY: 74276
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ClinVar
Significance: Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Jan 26, 2023 | See Variant Classification Assertion Criteria. - |
Microcephaly-intellectual disability-sensorineural hearing loss-epilepsy-abnormal muscle tone syndrome Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Oct 27, 2022 | - - |
Computational scores
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at