rs763749443
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_025137.4(SPG11):c.3502A>G(p.Asn1168Asp) variant causes a missense change. The variant allele was found at a frequency of 0.00000274 in 1,461,486 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. N1168K) has been classified as Uncertain significance.
Frequency
Consequence
NM_025137.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SPG11 | NM_025137.4 | c.3502A>G | p.Asn1168Asp | missense_variant | 20/40 | ENST00000261866.12 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SPG11 | ENST00000261866.12 | c.3502A>G | p.Asn1168Asp | missense_variant | 20/40 | 1 | NM_025137.4 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251352Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135858
GnomAD4 exome AF: 0.00000274 AC: 4AN: 1461486Hom.: 0 Cov.: 30 AF XY: 0.00000413 AC XY: 3AN XY: 727048
GnomAD4 genome ? Cov.: 32
ClinVar
Submissions by phenotype
Hereditary spastic paraplegia 11 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Mar 12, 2020 | 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. Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals with SPG11-related disease. This variant is present in population databases (rs763749443, ExAC 0.002%). This sequence change replaces asparagine with aspartic acid at codon 1168 of the SPG11 protein (p.Asn1168Asp). The asparagine residue is highly conserved and there is a small physicochemical difference between asparagine and aspartic acid. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at