15-64963676-C-T
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_016630.7(SPG21):c.871G>A(p.Ala291Thr) variant causes a missense change. The variant allele was found at a frequency of 0.0000186 in 1,614,048 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. A291A) has been classified as Likely benign.
Frequency
Consequence
NM_016630.7 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 rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
SPG21 | NM_016630.7 | c.871G>A | p.Ala291Thr | missense_variant | Exon 9 of 9 | ENST00000204566.7 | NP_057714.1 | |
SPG21 | NM_001127889.5 | c.871G>A | p.Ala291Thr | missense_variant | Exon 9 of 9 | NP_001121361.1 | ||
SPG21 | NM_001127890.5 | c.790G>A | p.Ala264Thr | missense_variant | Exon 8 of 8 | NP_001121362.1 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000131 AC: 2AN: 152216Hom.: 0 Cov.: 32
GnomAD4 exome AF: 0.0000192 AC: 28AN: 1461832Hom.: 0 Cov.: 31 AF XY: 0.0000151 AC XY: 11AN XY: 727228
GnomAD4 genome AF: 0.0000131 AC: 2AN: 152216Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74370
ClinVar
Submissions by phenotype
not specified Uncertain:1
The c.871G>A (p.A291T) alteration is located in exon 9 (coding exon 8) of the SPG21 gene. This alteration results from a G to A substitution at nucleotide position 871, causing the alanine (A) at amino acid position 291 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at