chr15-50719981-G-A
Variant summary
Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong
The NM_032802.4(SPPL2A):c.1447C>T(p.Arg483Cys) variant causes a missense change. The variant allele was found at a frequency of 0.0000298 in 1,613,186 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic 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. R483H) has been classified as Uncertain significance.
Frequency
Consequence
NM_032802.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_pathogenic. Variant got 6 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SPPL2A | NM_032802.4 | c.1447C>T | p.Arg483Cys | missense_variant | 14/15 | ENST00000261854.10 | |
SPPL2A | XM_005254722.4 | c.1501C>T | p.Arg501Cys | missense_variant | 15/16 | ||
SPPL2A | XM_017022680.2 | c.1381+2143C>T | intron_variant | ||||
SPPL2A | XM_017022681.2 | c.1327+2143C>T | intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SPPL2A | ENST00000261854.10 | c.1447C>T | p.Arg483Cys | missense_variant | 14/15 | 1 | NM_032802.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000132 AC: 2AN: 151996Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000199 AC: 5AN: 250932Hom.: 0 AF XY: 0.0000221 AC XY: 3AN XY: 135624
GnomAD4 exome AF: 0.0000315 AC: 46AN: 1461190Hom.: 0 Cov.: 30 AF XY: 0.0000261 AC XY: 19AN XY: 726944
GnomAD4 genome ? AF: 0.0000132 AC: 2AN: 151996Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74232
ClinVar
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Nov 28, 2023 | This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 483 of the SPPL2A protein (p.Arg483Cys). This variant is present in population databases (rs748291215, gnomAD 0.02%). This variant has not been reported in the literature in individuals affected with SPPL2A-related conditions. An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. 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