rs769885715
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate
The NM_033629.6(TREX1):āc.923C>Gā(p.Ser308Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000707 in 1,612,768 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 Uncertain significance (ā ā ).
Frequency
Consequence
NM_033629.6 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TREX1 | NM_033629.6 | c.923C>G | p.Ser308Cys | missense_variant | 2/2 | ENST00000625293.3 | |
ATRIP | NM_130384.3 | c.*2024C>G | 3_prime_UTR_variant | 13/13 | ENST00000320211.10 | ||
ATRIP-TREX1 | NR_153405.1 | n.4232C>G | non_coding_transcript_exon_variant | 15/15 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TREX1 | ENST00000625293.3 | c.923C>G | p.Ser308Cys | missense_variant | 2/2 | NM_033629.6 | P1 | ||
ATRIP | ENST00000320211.10 | c.*2024C>G | 3_prime_UTR_variant | 13/13 | 1 | NM_130384.3 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000788 AC: 12AN: 152206Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000401 AC: 10AN: 249512Hom.: 0 AF XY: 0.0000296 AC XY: 4AN XY: 135066
GnomAD4 exome AF: 0.0000698 AC: 102AN: 1460562Hom.: 0 Cov.: 33 AF XY: 0.0000743 AC XY: 54AN XY: 726450
GnomAD4 genome ? AF: 0.0000788 AC: 12AN: 152206Hom.: 0 Cov.: 33 AF XY: 0.0000538 AC XY: 4AN XY: 74354
ClinVar
Submissions by phenotype
Systemic lupus erythematosus;C0024145: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 | Fulgent Genetics, Fulgent Genetics | Jul 30, 2021 | - - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Aug 01, 2016 | - - |
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 | Jan 29, 2024 | This sequence change replaces serine, which is neutral and polar, with cysteine, which is neutral and slightly polar, at codon 308 of the TREX1 protein (p.Ser308Cys). This variant is present in population databases (rs769885715, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with TREX1-related conditions. ClinVar contains an entry for this variant (Variation ID: 374471). 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. 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. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at