rs886043118
Variant summary
Our verdict is Pathogenic. Variant got 18 ACMG points: 18P and 0B. PVS1PM2PP5_Very_Strong
The NM_007315.4(STAT1):c.88del(p.Ile30SerfsTer9) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,740 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Pathogenic (★★).
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 6.8e-7 ( 0 hom. )
Consequence
STAT1
NM_007315.4 frameshift
NM_007315.4 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 3.53
Genes affected
STAT1 (HGNC:11362): (signal transducer and activator of transcription 1) The protein encoded by this gene is a member of the STAT protein family. In response to cytokines and growth factors, STAT family members are phosphorylated by the receptor associated kinases, and then form homo- or heterodimers that translocate to the cell nucleus where they act as transcription activators. The protein encoded by this gene can be activated by various ligands including interferon-alpha, interferon-gamma, EGF, PDGF and IL6. This protein mediates the expression of a variety of genes, which is thought to be important for cell viability in response to different cell stimuli and pathogens. The protein plays an important role in immune responses to viral, fungal and mycobacterial pathogens. Mutations in this gene are associated with Immunodeficiency 31B, 31A, and 31C. [provided by RefSeq, Jun 2020]
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ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 18 ACMG points.
PVS1
?
Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant located near the start codon (<100nt), not predicted to undergo nonsense mediated mRNA decay. There are 143 pathogenic variants in the truncated region.
PM2
?
Very rare variant in population databases, with high coverage;
PP5
?
Variant 2-191009915-AT-A is Pathogenic according to our data. Variant chr2-191009915-AT-A is described in ClinVar as [Pathogenic]. Clinvar id is 285493.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
STAT1 | NM_007315.4 | c.88del | p.Ile30SerfsTer9 | frameshift_variant | 3/25 | ENST00000361099.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
STAT1 | ENST00000361099.8 | c.88del | p.Ile30SerfsTer9 | frameshift_variant | 3/25 | 1 | NM_007315.4 | P4 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
Cov.:
32
GnomAD4 exome AF: 6.84e-7 AC: 1AN: 1461740Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1AN XY: 727160
GnomAD4 exome
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31
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727160
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GnomAD4 genome ? Cov.: 32
GnomAD4 genome
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Cov.:
32
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Dec 16, 2015 | - - |
Immunodeficiency 31B Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Victorian Clinical Genetics Services, Murdoch Childrens Research Institute | Jul 24, 2015 | This deletion of a single base pair results in the introduction of a premature stop codon at position 30, NP_009330.1, p.(Ile30*). This is a novel variant, not present in disease or population databases. It was identified in the homozygous state in this patient, and the parents were confirmed to be carriers. Flow cytometric analysis of STAT-1 phosphorylation after treatment with IFN-alpha and IFN-gamma confirmed absent phosphorylation. - |
Computational scores
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at