rs771610641
Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2BP4_StrongBS1_Supporting
The NM_002618.4(PEX13):c.89T>C(p.Phe30Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000836 in 1,550,418 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 (★★).
Frequency
Consequence
NM_002618.4 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: 0.000565 AC: 86AN: 152214Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000510 AC: 77AN: 150968Hom.: 0 AF XY: 0.000619 AC XY: 50AN XY: 80712
GnomAD4 exome AF: 0.000865 AC: 1210AN: 1398086Hom.: 0 Cov.: 30 AF XY: 0.000863 AC XY: 595AN XY: 689570
GnomAD4 genome AF: 0.000565 AC: 86AN: 152332Hom.: 0 Cov.: 32 AF XY: 0.000644 AC XY: 48AN XY: 74496
ClinVar
Submissions by phenotype
not provided Uncertain:2
In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge -
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Peroxisome biogenesis disorder 11A (Zellweger) Uncertain:2
This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. -
This sequence change replaces phenylalanine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 30 of the PEX13 protein (p.Phe30Ser). This variant is present in population databases (rs771610641, gnomAD 0.1%), and has an allele count higher than expected for a pathogenic variant. This variant has not been reported in the literature in individuals affected with PEX13-related conditions. ClinVar contains an entry for this variant (Variation ID: 500639). 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. 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. -
Inborn genetic diseases Uncertain:1
The c.89T>C (p.F30S) alteration is located in exon 1 (coding exon 1) of the PEX13 gene. This alteration results from a T to C substitution at nucleotide position 89, causing the phenylalanine (F) at amino acid position 30 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -
PEX13-related disorder Uncertain:1
The PEX13 c.89T>C variant is predicted to result in the amino acid substitution p.Phe30Ser. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.091% of alleles in individuals of European (Finnish) descent in gnomAD. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. -
Peroxisome biogenesis disorder 11A (Zellweger);C3554001:Peroxisome biogenesis disorder 11B Uncertain:1
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at