rs374771569
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_145207.3(SPATA5):c.436G>A(p.Val146Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000647 in 1,591,388 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).
Frequency
Consequence
NM_145207.3 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SPATA5 | NM_145207.3 | c.436G>A | p.Val146Met | missense_variant | 3/16 | ENST00000274008.5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
AFG2A | ENST00000274008.5 | c.436G>A | p.Val146Met | missense_variant | 3/16 | 1 | NM_145207.3 | P1 | |
AFG2A | ENST00000422835.2 | n.478G>A | non_coding_transcript_exon_variant | 3/15 | 1 | ||||
AFG2A | ENST00000675612.1 | c.433G>A | p.Val145Met | missense_variant | 3/17 | ||||
AFG2A | ENST00000674886.1 | n.498G>A | non_coding_transcript_exon_variant | 3/11 |
Frequencies
GnomAD3 genomes ? AF: 0.000296 AC: 45AN: 152136Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000693 AC: 16AN: 230850Hom.: 0 AF XY: 0.0000797 AC XY: 10AN XY: 125486
GnomAD4 exome AF: 0.0000403 AC: 58AN: 1439134Hom.: 1 Cov.: 30 AF XY: 0.0000448 AC XY: 32AN XY: 714968
GnomAD4 genome ? AF: 0.000296 AC: 45AN: 152254Hom.: 0 Cov.: 32 AF XY: 0.000309 AC XY: 23AN XY: 74452
ClinVar
Submissions by phenotype
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jun 26, 2023 | The c.436G>A (p.V146M) alteration is located in exon 3 (coding exon 3) of the SPATA5 gene. This alteration results from a G to A substitution at nucleotide position 436, causing the valine (V) at amino acid position 146 to be replaced by a methionine (M). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Apr 28, 2023 | In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge - |
Microcephaly-intellectual disability-sensorineural hearing loss-epilepsy-abnormal muscle tone syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Nov 01, 2022 | This sequence change replaces valine, which is neutral and non-polar, with methionine, which is neutral and non-polar, at codon 146 of the SPATA5 protein (p.Val146Met). This variant is present in population databases (rs374771569, gnomAD 0.08%). 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: 475731). 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on 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