chr16-89546731-G-A
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 4P and 1B. PM1PM2BP4
The NM_003119.4(SPG7):c.1523G>A(p.Arg508His) variant causes a missense change. The variant allele was found at a frequency of 0.0000403 in 1,613,192 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 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. R508C) has been classified as Uncertain significance.
Frequency
Consequence
NM_003119.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SPG7 | NM_003119.4 | c.1523G>A | p.Arg508His | missense_variant | 11/17 | ENST00000645818.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SPG7 | ENST00000645818.2 | c.1523G>A | p.Arg508His | missense_variant | 11/17 | NM_003119.4 | P2 |
Frequencies
GnomAD3 genomes AF: 0.0000329 AC: 5AN: 152178Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000756 AC: 19AN: 251476Hom.: 0 AF XY: 0.0000809 AC XY: 11AN XY: 135916
GnomAD4 exome AF: 0.0000411 AC: 60AN: 1460896Hom.: 0 Cov.: 32 AF XY: 0.0000413 AC XY: 30AN XY: 726830
GnomAD4 genome AF: 0.0000328 AC: 5AN: 152296Hom.: 0 Cov.: 32 AF XY: 0.0000537 AC XY: 4AN XY: 74470
ClinVar
Submissions by phenotype
Hereditary spastic paraplegia Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Genome Diagnostics Laboratory, The Hospital for Sick Children | Apr 01, 2019 | - - |
Hereditary spastic paraplegia 7 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jul 11, 2022 | 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 (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. ClinVar contains an entry for this variant (Variation ID: 570831). This missense change has been observed in individual(s) with hereditary spastic paraplegia (PMID: 27217339). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 508 of the SPG7 protein (p.Arg508His). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at