chr16-89553132-T-A
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 4P and 4B. PM1PM2BP4_Strong
The NM_003119.4(SPG7):c.1933T>A(p.Ser645Thr) variant causes a missense change. The variant allele was found at a frequency of 0.000812 in 1,606,910 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 11/19 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
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 |
---|---|---|---|---|---|---|---|
SPG7 | NM_003119.4 | c.1933T>A | p.Ser645Thr | missense_variant | 14/17 | ENST00000645818.2 | |
SPG7 | NM_001363850.1 | c.1933T>A | p.Ser645Thr | missense_variant | 14/18 | ||
SPG7 | XM_047434537.1 | c.1060T>A | p.Ser354Thr | missense_variant | 9/13 | ||
SPG7 | XM_047434540.1 | c.619T>A | p.Ser207Thr | missense_variant | 6/9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SPG7 | ENST00000645818.2 | c.1933T>A | p.Ser645Thr | missense_variant | 14/17 | NM_003119.4 | P2 |
Frequencies
GnomAD3 genomes AF: 0.000736 AC: 112AN: 152192Hom.: 1 Cov.: 33
GnomAD3 exomes AF: 0.000818 AC: 191AN: 233420Hom.: 0 AF XY: 0.000687 AC XY: 87AN XY: 126710
GnomAD4 exome AF: 0.000820 AC: 1193AN: 1454600Hom.: 0 Cov.: 31 AF XY: 0.000799 AC XY: 578AN XY: 723048
GnomAD4 genome AF: 0.000735 AC: 112AN: 152310Hom.: 1 Cov.: 33 AF XY: 0.000779 AC XY: 58AN XY: 74484
ClinVar
Submissions by phenotype
Hereditary spastic paraplegia Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Genome Diagnostics Laboratory, The Hospital for Sick Children | Dec 01, 2018 | - - |
Uncertain significance, criteria provided, single submitter | research | Unit for Genetic & Epidemiological Research on Neurological Disorders, Instituto de Investigação e Inovação em Saúde | Mar 07, 2017 | - - |
not provided Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Jun 01, 2023 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Jul 08, 2021 | Identified as heterozygous without a second variant in SPG7 in several individuals with hereditary spastic paraplegia; in one family, the authors did not consider the variant disease causing as it was absent in at least one affected family member (Elleuch et al., 2006; Arnoldi et al., 2008; Morais et al., 2017).; In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 22571692, 27535533, 28832565, 18200586, 16534102) - |
Hereditary spastic paraplegia 7 Uncertain:1Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Dec 12, 2023 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Apr 27, 2017 | This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. However, the evidence from the literature, in combination with allele frequency data from public databases where available, was not sufficient to rule this variant in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at