rs763737752
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_145207.3(SPATA5):āc.1963C>Gā(p.Arg655Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,850 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (ā ). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R655Q) has been classified as Uncertain significance.
Frequency
Consequence
NM_145207.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SPATA5 | NM_145207.3 | c.1963C>G | p.Arg655Gly | missense_variant | 11/16 | ENST00000274008.5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
AFG2A | ENST00000274008.5 | c.1963C>G | p.Arg655Gly | missense_variant | 11/16 | 1 | NM_145207.3 | P1 | |
AFG2A | ENST00000422835.2 | n.2005C>G | non_coding_transcript_exon_variant | 11/15 | 1 | ||||
AFG2A | ENST00000675612.1 | c.2032C>G | p.Arg678Gly | missense_variant | 12/17 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD4 exome AF: 6.84e-7 AC: 1AN: 1461850Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0AN XY: 727222
GnomAD4 genome ? Cov.: 32
ClinVar
Submissions by phenotype
Microcephaly-intellectual disability-sensorineural hearing loss-epilepsy-abnormal muscle tone syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Aug 31, 2021 | This sequence change replaces arginine with glycine at codon 655 of the SPATA5 protein (p.Arg655Gly). The arginine residue is highly conserved and there is a moderate physicochemical difference between arginine and glycine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals affected with SPATA5-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive. 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:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at