rs76642637
Variant summary
Our verdict is Pathogenic. Variant got 16 ACMG points: 16P and 0B. PVS1PP5_Very_Strong
The NM_033629.6(TREX1):βc.500delβ(p.Ser167ThrfsTer13) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000558 in 1,613,946 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Pathogenic (β β ). Synonymous variant affecting the same amino acid position (i.e. S167S) has been classified as Likely benign.
Frequency
Consequence
NM_033629.6 frameshift
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 16 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TREX1 | NM_033629.6 | c.500del | p.Ser167ThrfsTer13 | frameshift_variant | 2/2 | ENST00000625293.3 | |
ATRIP | NM_130384.3 | c.*1601del | 3_prime_UTR_variant | 13/13 | ENST00000320211.10 | ||
ATRIP-TREX1 | NR_153405.1 | n.3809del | non_coding_transcript_exon_variant | 15/15 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TREX1 | ENST00000625293.3 | c.500del | p.Ser167ThrfsTer13 | frameshift_variant | 2/2 | NM_033629.6 | P1 | ||
ATRIP | ENST00000320211.10 | c.*1601del | 3_prime_UTR_variant | 13/13 | 1 | NM_130384.3 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000263 AC: 4AN: 152222Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.00000399 AC: 1AN: 250420Hom.: 0 AF XY: 0.00000738 AC XY: 1AN XY: 135410
GnomAD4 exome AF: 0.00000342 AC: 5AN: 1461724Hom.: 0 Cov.: 31 AF XY: 0.00000275 AC XY: 2AN XY: 727164
GnomAD4 genome AF: 0.0000263 AC: 4AN: 152222Hom.: 0 Cov.: 33 AF XY: 0.0000403 AC XY: 3AN XY: 74374
ClinVar
Submissions by phenotype
not provided Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Jul 12, 2016 | - - |
Chilblain lupus 1;C0796126:Aicardi-Goutieres syndrome 1;C1860518:Retinal vasculopathy with cerebral leukoencephalopathy and systemic manifestations Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Jan 01, 2023 | For these reasons, this variant has been classified as Pathogenic. This variant disrupts a region of the TREX1 protein in which other variant(s) (p.W210*) have been determined to be pathogenic (PMID: 26938784; Invitae). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. ClinVar contains an entry for this variant (Variation ID: 126389). This premature translational stop signal has been observed in individual(s) with autosomal recessive Aicardi-Goutieres syndrome (PMID: 17846997, 20131292). This variant is present in population databases (rs76642637, gnomAD 0.01%). This sequence change creates a premature translational stop signal (p.Ser167Thrfs*13) in the TREX1 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 148 amino acid(s) of the TREX1 protein. - |
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