rs76224909
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 1P and 0B. PP5
The NM_033629.6(TREX1):āc.907A>Cā(p.Thr303Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000149 in 1,613,658 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T303I) has been classified as Uncertain significance.
Frequency
Consequence
NM_033629.6 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TREX1 | NM_033629.6 | c.907A>C | p.Thr303Pro | missense_variant | 2/2 | ENST00000625293.3 | |
ATRIP | NM_130384.3 | c.*2008A>C | 3_prime_UTR_variant | 13/13 | ENST00000320211.10 | ||
ATRIP-TREX1 | NR_153405.1 | n.4216A>C | non_coding_transcript_exon_variant | 15/15 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TREX1 | ENST00000625293.3 | c.907A>C | p.Thr303Pro | missense_variant | 2/2 | NM_033629.6 | P1 | ||
ATRIP | ENST00000320211.10 | c.*2008A>C | 3_prime_UTR_variant | 13/13 | 1 | NM_130384.3 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00000657 AC: 1AN: 152194Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000200 AC: 5AN: 250432Hom.: 0 AF XY: 0.00000738 AC XY: 1AN XY: 135530
GnomAD4 exome AF: 0.0000157 AC: 23AN: 1461464Hom.: 0 Cov.: 33 AF XY: 0.0000165 AC XY: 12AN XY: 727040
GnomAD4 genome ? AF: 0.00000657 AC: 1AN: 152194Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0AN XY: 74348
ClinVar
Submissions by phenotype
not provided Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Institute for Clinical Genetics, University Hospital TU Dresden, University Hospital TU Dresden | Nov 03, 2021 | - - |
Chilblain lupus 1;C0796126:Aicardi-Goutieres syndrome 1;C1860518:Retinal vasculopathy with cerebral leukoencephalopathy and systemic manifestations Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Aug 18, 2023 | 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. This sequence change replaces threonine, which is neutral and polar, with proline, which is neutral and non-polar, at codon 303 of the TREX1 protein (p.Thr303Pro). This variant is present in population databases (rs76224909, gnomAD 0.004%). This missense change has been observed in individual(s) with Aicardi-Goutieres syndrome (PMID: 17846997, 21270825). ClinVar contains an entry for this variant (Variation ID: 126394). 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. - |
Aicardi-Goutieres syndrome 1 Other:1
not provided, no classification provided | literature only | GeneReviews | - | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at