rs769181441
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PM5
The NM_145207.3(SPATA5):c.1441A>T(p.Met481Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000622 in 1,447,010 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. M481T) has been classified as Likely pathogenic.
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.1441A>T | p.Met481Leu | missense_variant | 8/16 | ENST00000274008.5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
AFG2A | ENST00000274008.5 | c.1441A>T | p.Met481Leu | missense_variant | 8/16 | 1 | NM_145207.3 | P1 | |
AFG2A | ENST00000422835.2 | n.1483A>T | non_coding_transcript_exon_variant | 8/15 | 1 | ||||
AFG2A | ENST00000675612.1 | c.1438A>T | p.Met480Leu | missense_variant | 8/17 | ||||
AFG2A | ENST00000674886.1 | n.1503A>T | non_coding_transcript_exon_variant | 8/11 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 exomes AF: 0.0000248 AC: 6AN: 241748Hom.: 0 AF XY: 0.0000153 AC XY: 2AN XY: 130506
GnomAD4 exome AF: 0.00000622 AC: 9AN: 1447010Hom.: 0 Cov.: 30 AF XY: 0.00000556 AC XY: 4AN XY: 719210
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 | Oct 26, 2022 | This sequence change replaces methionine, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 481 of the SPATA5 protein (p.Met481Leu). This variant is present in population databases (rs769181441, gnomAD 0.02%). 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: 475719). 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 not 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