1-2406576-T-C
Variant summary
Our verdict is Benign. Variant got -18 ACMG points: 2P and 20B. PM1BP4_StrongBP6_Very_StrongBS1BS2
The NM_002617.4(PEX10):āc.820A>Gā(p.Thr274Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0227 in 1,613,202 control chromosomes in the GnomAD database, including 507 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (ā ā ). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T274I) has been classified as Uncertain significance.
Frequency
Consequence
NM_002617.4 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Benign. Variant got -18 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PEX10 | NM_002617.4 | c.820A>G | p.Thr274Ala | missense_variant | 5/6 | ENST00000447513.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PEX10 | ENST00000447513.7 | c.820A>G | p.Thr274Ala | missense_variant | 5/6 | 1 | NM_002617.4 | P4 |
Frequencies
GnomAD3 genomes AF: 0.0188 AC: 2851AN: 152044Hom.: 42 Cov.: 33
GnomAD3 exomes AF: 0.0203 AC: 5069AN: 250264Hom.: 85 AF XY: 0.0205 AC XY: 2781AN XY: 135646
GnomAD4 exome AF: 0.0231 AC: 33805AN: 1461040Hom.: 465 Cov.: 34 AF XY: 0.0230 AC XY: 16719AN XY: 726848
GnomAD4 genome AF: 0.0187 AC: 2850AN: 152162Hom.: 42 Cov.: 33 AF XY: 0.0178 AC XY: 1323AN XY: 74384
ClinVar
Submissions by phenotype
not specified Benign:4
Benign, no assertion criteria provided | clinical testing | Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen | - | - - |
Benign, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Nov 23, 2014 | - - |
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Likely benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Mar 29, 2016 | Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency in ESP (all): 272/13006=2% - |
Peroxisome biogenesis disorder 6A (Zellweger) Benign:2
Likely benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Apr 27, 2017 | This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to determine this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. - |
Benign, criteria provided, single submitter | research | Broad Center for Mendelian Genomics, Broad Institute of MIT and Harvard | - | The heterozygous p.Thr294Ala variant in PEX10 has been identified in cis with a frameshift mutation and in an individual with Zellweger syndrome (PMID: 19127411). This variant has been identified in >2% of European (non-Finnish) chromosomes and 36 homozygotes by ExAC (http://gnomad.broadinstitute.org/). In summary, this variant meets criteria to be classified as benign for autosomal recessive Zellweger syndrome. - |
not provided Benign:2
Likely benign, no assertion criteria provided | clinical testing | Genome Diagnostics Laboratory, University Medical Center Utrecht | - | - - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Oct 01, 2020 | This variant is associated with the following publications: (PMID: 15542397, 27535533, 19127411) - |
Peroxisome biogenesis disorder, complementation group 7 Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Feb 01, 2024 | - - |
Zellweger spectrum disorders Benign:1
Benign, no assertion criteria provided | clinical testing | Natera, Inc. | Nov 26, 2019 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at