rs201543030
Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 0P and 3B. BP4_ModerateBS2_Supporting
The NM_003119.4(SPG7):c.1267G>A(p.Gly423Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000855 in 1,613,766 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_003119.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SPG7 | NM_003119.4 | c.1267G>A | p.Gly423Ser | missense_variant | 9/17 | ENST00000645818.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SPG7 | ENST00000645818.2 | c.1267G>A | p.Gly423Ser | missense_variant | 9/17 | NM_003119.4 | P2 |
Frequencies
GnomAD3 genomes ? AF: 0.000223 AC: 34AN: 152180Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000599 AC: 15AN: 250616Hom.: 0 AF XY: 0.0000295 AC XY: 4AN XY: 135724
GnomAD4 exome AF: 0.0000691 AC: 101AN: 1461468Hom.: 3 Cov.: 32 AF XY: 0.0000633 AC XY: 46AN XY: 727036
GnomAD4 genome ? AF: 0.000243 AC: 37AN: 152298Hom.: 1 Cov.: 33 AF XY: 0.000215 AC XY: 16AN XY: 74480
ClinVar
Submissions by phenotype
not provided Uncertain:3
Uncertain significance, criteria provided, single submitter | clinical testing | Athena Diagnostics | Dec 21, 2022 | Available data are insufficient to determine the clinical significance of the variant at this time. The frequency of this variant in the general population is uninformative in assessment of its pathogenicity (http://gnomad.broadinstitute.org). Computational tools predict that this variant is not damaging. The variant is located in a region that is considered important for protein function and/or structure. - |
Uncertain significance, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Jul 01, 2019 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Jul 12, 2019 | In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; Has not been previously published as pathogenic or benign to our knowledge - |
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Women's Health and Genetics/Laboratory Corporation of America, LabCorp | Dec 22, 2023 | Variant summary: SPG7 c.1267G>A (p.Gly423Ser) results in a non-conservative amino acid change located in the AAA+ ATPase domain (IPR003593) of the encoded protein sequence. Three of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 6e-05 in 250616 control chromosomes. To our knowledge, no occurrence of c.1267G>A in individuals affected with Hereditary Spastic Paraplegia 7 and no experimental evidence demonstrating its impact on protein function have been reported. Four submitters have cited clinical-significance assessments for this variant to ClinVar after 2014 (VUS, n=3; Likely benign, n=1). Based on the evidence outlined above, the variant was classified as uncertain significance. - |
Hereditary spastic paraplegia 7 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Oct 14, 2023 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at