rs141168255
Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 1P and 4B. PP3BS2
The NM_014467.3(SRPX2):āc.248T>Cā(p.Leu83Pro) variant causes a missense change. The variant allele was found at a frequency of 0.000184 in 1,210,208 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 73 hemizygotes in GnomAD. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_014467.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -3 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000714 AC: 8AN: 112035Hom.: 0 Cov.: 23 AF XY: 0.0000292 AC XY: 1AN XY: 34195
GnomAD3 exomes AF: 0.0000818 AC: 15AN: 183425Hom.: 0 AF XY: 0.0000442 AC XY: 3AN XY: 67869
GnomAD4 exome AF: 0.000196 AC: 215AN: 1098173Hom.: 0 Cov.: 31 AF XY: 0.000198 AC XY: 72AN XY: 363529
GnomAD4 genome AF: 0.0000714 AC: 8AN: 112035Hom.: 0 Cov.: 23 AF XY: 0.0000292 AC XY: 1AN XY: 34195
ClinVar
Submissions by phenotype
not provided Uncertain:1Benign:1
SRPX2: BS2 -
p.Leu83Pro (CTG>CCG): c.248 T>C in exon 4 o the SRPX2 gene (NM_014467.2) The L83P variant has not been published as a mutation, nor has it been reported as a benign polymorphism to our knowledge. The L83P variant was not observed with any significant frequency in approximately 5,400 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project. The L83P variant is a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some properties. This substitution alters a highly conserved position in the predicted Sushi 1 domain of the SRPX2 protein. Additionally, in silico analysis predicts this variant is probably damaging to the protein structure/function. Based on the currently available information, it is unclear whether this variant is a pathogenic mutation or a rare benign variant. The variant is found in EPILEPSY panel(s). -
not specified Uncertain:1
- -
Rolandic epilepsy, intellectual disability, and speech dyspraxia, X-linked Uncertain:1
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 disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has not been reported in the literature in individuals with SRPX2-related conditions. ClinVar contains an entry for this variant (Variation ID: 207388). This variant is present in population databases (rs141168255, ExAC 0.006%). This sequence change replaces leucine with proline at codon 83 of the SRPX2 protein (p.Leu83Pro). The leucine residue is highly 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