rs750306995
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_003119.4(SPG7):c.1654G>A(p.Val552Ile) variant causes a missense change. The variant allele was found at a frequency of 0.000119 in 1,603,940 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★). Synonymous variant affecting the same amino acid position (i.e. V552V) has been classified as Likely benign.
Frequency
Consequence
NM_003119.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SPG7 | NM_003119.4 | c.1654G>A | p.Val552Ile | missense_variant | 12/17 | ENST00000645818.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SPG7 | ENST00000645818.2 | c.1654G>A | p.Val552Ile | missense_variant | 12/17 | NM_003119.4 | P2 |
Frequencies
GnomAD3 genomes ? AF: 0.0000394 AC: 6AN: 152242Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000617 AC: 15AN: 243116Hom.: 0 AF XY: 0.0000529 AC XY: 7AN XY: 132338
GnomAD4 exome AF: 0.000127 AC: 185AN: 1451698Hom.: 0 Cov.: 29 AF XY: 0.000115 AC XY: 83AN XY: 722616
GnomAD4 genome ? AF: 0.0000394 AC: 6AN: 152242Hom.: 0 Cov.: 33 AF XY: 0.0000807 AC XY: 6AN XY: 74380
ClinVar
Submissions by phenotype
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | May 26, 2022 | The c.1654G>A (p.V552I) alteration is located in exon 12 (coding exon 12) of the SPG7 gene. This alteration results from a G to A substitution at nucleotide position 1654, causing the valine (V) at amino acid position 552 to be replaced by an isoleucine (I). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Hereditary spastic paraplegia 7 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Aug 13, 2022 | This sequence change replaces valine, which is neutral and non-polar, with isoleucine, which is neutral and non-polar, at codon 552 of the SPG7 protein (p.Val552Ile). This variant is present in population databases (rs750306995, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with SPG7-related conditions. ClinVar contains an entry for this variant (Variation ID: 533733). 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 SPG7 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