15-44626347-T-C
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_025137.4(SPG11):āc.2228A>Gā(p.Glu743Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000161 in 1,612,296 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ).
Frequency
Consequence
NM_025137.4 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 | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
SPG11 | NM_025137.4 | c.2228A>G | p.Glu743Gly | missense_variant | 11/40 | ENST00000261866.12 | NP_079413.3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
SPG11 | ENST00000261866.12 | c.2228A>G | p.Glu743Gly | missense_variant | 11/40 | 1 | NM_025137.4 | ENSP00000261866.7 |
Frequencies
GnomAD3 genomes AF: 0.0000197 AC: 3AN: 152218Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000200 AC: 5AN: 250056Hom.: 0 AF XY: 0.0000221 AC XY: 3AN XY: 135504
GnomAD4 exome AF: 0.0000158 AC: 23AN: 1460078Hom.: 0 Cov.: 31 AF XY: 0.0000165 AC XY: 12AN XY: 726334
GnomAD4 genome AF: 0.0000197 AC: 3AN: 152218Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1AN XY: 74370
ClinVar
Submissions by phenotype
Hereditary spastic paraplegia 11 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Sep 12, 2022 | This sequence change replaces glutamic acid, which is acidic and polar, with glycine, which is neutral and non-polar, at codon 743 of the SPG11 protein (p.Glu743Gly). This variant is present in population databases (rs199617257, gnomAD 0.003%). This variant has not been reported in the literature in individuals affected with SPG11-related conditions. ClinVar contains an entry for this variant (Variation ID: 578059). 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 SPG11 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