rs148135198
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate
The NM_145207.3(SPATA5):c.1502G>A(p.Arg501His) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000118 in 1,609,966 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R501C) 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 4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SPATA5 | NM_145207.3 | c.1502G>A | p.Arg501His | missense_variant | 9/16 | ENST00000274008.5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
AFG2A | ENST00000274008.5 | c.1502G>A | p.Arg501His | missense_variant | 9/16 | 1 | NM_145207.3 | P1 | |
AFG2A | ENST00000422835.2 | n.1544G>A | non_coding_transcript_exon_variant | 9/15 | 1 | ||||
AFG2A | ENST00000675612.1 | c.1499G>A | p.Arg500His | missense_variant | 9/17 | ||||
AFG2A | ENST00000674886.1 | n.1564G>A | non_coding_transcript_exon_variant | 9/11 |
Frequencies
GnomAD3 genomes ? AF: 0.0000658 AC: 10AN: 151970Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00000805 AC: 2AN: 248370Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 134338
GnomAD4 exome AF: 0.00000617 AC: 9AN: 1457996Hom.: 0 Cov.: 31 AF XY: 0.00000414 AC XY: 3AN XY: 725288
GnomAD4 genome ? AF: 0.0000658 AC: 10AN: 151970Hom.: 0 Cov.: 32 AF XY: 0.0000809 AC XY: 6AN XY: 74182
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 | Jul 13, 2022 | This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 501 of the SPATA5 protein (p.Arg501His). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. 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: 542387). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt SPATA5 protein function. 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