rs114854791
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_003119.4(SPG7):c.220G>A(p.Gly74Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000759 in 1,607,286 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Synonymous variant affecting the same amino acid position (i.e. G74G) has been classified as Uncertain significance.
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.220G>A | p.Gly74Arg | missense_variant | 2/17 | ENST00000645818.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SPG7 | ENST00000645818.2 | c.220G>A | p.Gly74Arg | missense_variant | 2/17 | NM_003119.4 | P2 |
Frequencies
GnomAD3 genomes ? AF: 0.000212 AC: 32AN: 150732Hom.: 0 Cov.: 31
GnomAD3 exomes AF: 0.0000996 AC: 25AN: 251020Hom.: 0 AF XY: 0.000103 AC XY: 14AN XY: 135734
GnomAD4 exome AF: 0.0000618 AC: 90AN: 1456438Hom.: 0 Cov.: 34 AF XY: 0.0000635 AC XY: 46AN XY: 724836
GnomAD4 genome ? AF: 0.000212 AC: 32AN: 150848Hom.: 0 Cov.: 31 AF XY: 0.000258 AC XY: 19AN XY: 73584
ClinVar
Submissions by phenotype
not provided Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Apr 25, 2014 | p.Gly74Arg (GGG>AGG): c.220 G>A in exon 2 of the SPG7 gene (NM_003119.2). A variant of unknown significance has been identified in the SPG7 gene. The G74R variant has not been published as a mutation, nor has it been reported as a benign polymorphism to our knowledge. The G74R variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. This substitution occurs at a position that is mostly conserved across species; although, Arginine is present at this position in another species. In silico analysis predicts this variant is probably damaging to the protein structure/function. Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic mutation or a rare benign variant. The variant is found in MITONUC-MITOP panel(s). - |
Uncertain significance, criteria provided, single submitter | clinical testing | Athena Diagnostics | Apr 13, 2022 | - - |
Hereditary spastic paraplegia 7 Uncertain:1Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Apr 24, 2023 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Oct 31, 2018 | - - |
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Women's Health and Genetics/Laboratory Corporation of America, LabCorp | Feb 28, 2024 | Variant summary: SPG7 c.220G>A (p.Gly74Arg) results in a non-conservative amino acid change in the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 0.0001 in 251020 control chromosomes. To our knowledge, no occurrence of c.220G>A in individuals affected with Hereditary Spastic Paraplegia 7 and no experimental evidence demonstrating its impact on protein function have been reported. ClinVar contains an entry for this variant (Variation ID: 215213). Based on the evidence outlined above, the variant was classified as uncertain significance. - |
Hereditary spastic paraplegia Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Genome Diagnostics Laboratory, The Hospital for Sick Children | Dec 12, 2016 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at