16-89508449-T-C
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_003119.4(SPG7):āc.32T>Cā(p.Leu11Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000133 in 1,502,400 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 ). Synonymous variant affecting the same amino acid position (i.e. L11L) has been classified as Likely benign.
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.32T>C | p.Leu11Pro | missense_variant | 1/17 | ENST00000645818.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SPG7 | ENST00000645818.2 | c.32T>C | p.Leu11Pro | missense_variant | 1/17 | NM_003119.4 | P2 |
Frequencies
GnomAD3 genomes AF: 0.00000658 AC: 1AN: 151898Hom.: 0 Cov.: 33
GnomAD4 exome AF: 7.40e-7 AC: 1AN: 1350502Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0AN XY: 666140
GnomAD4 genome AF: 0.00000658 AC: 1AN: 151898Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0AN XY: 74208
ClinVar
Submissions by phenotype
Hereditary spastic paraplegia 7 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Apr 02, 2019 | 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. This variant has not been reported in the literature in individuals with SPG7-related conditions. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate insufficient coverage at this position in the ExAC database. This sequence change replaces leucine with proline at codon 11 of the SPG7 protein (p.Leu11Pro). The leucine residue is weakly conserved and there is a moderate physicochemical difference between leucine and proline. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at