rs55999987
Variant summary
Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2
The NM_033629.6(TREX1):āc.797A>Gā(p.Glu266Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00301 in 1,614,140 control chromosomes in the GnomAD database, including 9 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Synonymous variant affecting the same amino acid position (i.e. E266E) has been classified as Likely benign.
Frequency
Consequence
NM_033629.6 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -13 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TREX1 | NM_033629.6 | c.797A>G | p.Glu266Gly | missense_variant | 2/2 | ENST00000625293.3 | |
ATRIP | NM_130384.3 | c.*1898A>G | 3_prime_UTR_variant | 13/13 | ENST00000320211.10 | ||
ATRIP-TREX1 | NR_153405.1 | n.4106A>G | non_coding_transcript_exon_variant | 15/15 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TREX1 | ENST00000625293.3 | c.797A>G | p.Glu266Gly | missense_variant | 2/2 | NM_033629.6 | P1 | ||
ATRIP | ENST00000320211.10 | c.*1898A>G | 3_prime_UTR_variant | 13/13 | 1 | NM_130384.3 | P1 |
Frequencies
GnomAD3 genomes AF: 0.00175 AC: 266AN: 152160Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.00165 AC: 416AN: 251436Hom.: 1 AF XY: 0.00168 AC XY: 229AN XY: 135912
GnomAD4 exome AF: 0.00314 AC: 4591AN: 1461862Hom.: 9 Cov.: 33 AF XY: 0.00310 AC XY: 2255AN XY: 727240
GnomAD4 genome AF: 0.00175 AC: 266AN: 152278Hom.: 0 Cov.: 33 AF XY: 0.00149 AC XY: 111AN XY: 74468
ClinVar
Submissions by phenotype
not provided Uncertain:3Benign:2
Uncertain significance, criteria provided, single submitter | clinical testing | Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics | Feb 09, 2017 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Sep 24, 2013 | - - |
Likely benign, no assertion criteria provided | clinical testing | Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC) | - | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Athena Diagnostics | Apr 23, 2018 | - - |
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Jan 01, 2024 | TREX1: BP4, BS2 - |
not specified Uncertain:2Benign:1
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Sep 28, 2016 | The E266G variant has not been published in association with Aicardi-Goutieres syndrome. However, the E266G variant has been published in association with systemic lupus erythematosus (SLE) (Namjou et al., 2011; Lee-Kirsch et al., 2007). Namjou et al., reports identifying the E266G variant in 5 patients of African decent diagnosed with SLE but not in ethnically matched controls (Namjou et al., 2011). This variant was also identified identified in members of the cohort of European decent but also within ethnically matched controls (Namjou et al., 2011). The NHLBI Exome Sequencing Project reports E266G was observed in 33/8600 (0.38%) alleles from individuals of European background, and the 1000 Genomes Project Consortium reports E266G was observed in 1/978 (0.1%) alleles from individuals of South Asian background. The E266G variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. This substitution occurs at a position that is not conserved. In silico analysis predicts this variant likely does not alter the protein structure/function. Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant. - |
Benign, no assertion criteria provided | clinical testing | Genome Diagnostics Laboratory, University Medical Center Utrecht | - | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital | Feb 06, 2024 | - - |
Aicardi Goutieres syndrome Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jun 14, 2016 | - - |
Retinal vasculopathy with cerebral leukoencephalopathy and systemic manifestations Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jun 14, 2016 | - - |
Chilblain lupus 1;C0796126:Aicardi-Goutieres syndrome 1;C1860518:Retinal vasculopathy with cerebral leukoencephalopathy and systemic manifestations Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 31, 2024 | - - |
Aicardi-Goutieres syndrome 1;C1860518:Retinal vasculopathy with cerebral leukoencephalopathy and systemic manifestations Benign:1
Likely benign, no assertion criteria provided | research | Institute of Neurology, Charite University of Medicine | Jun 04, 2022 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at