rs148775168
Variant names:
Your query was ambiguous. Multiple possible variants found:
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 5P and 2B. PM1PM2PP2BP4_Moderate
The NM_007315.4(STAT1):c.793A>T(p.Ile265Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.
Frequency
Genomes: not found (cov: 31)
Consequence
STAT1
NM_007315.4 missense
NM_007315.4 missense
Scores
2
17
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: 0.0820
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 Uncertain_significance. Variant got 3 ACMG points.
PM1
In a coiled_coil_region (size 181) in uniprot entity STAT1_HUMAN there are 33 pathogenic changes around while only 1 benign (97%) in NM_007315.4
PM2
Very rare variant in population databases, with high coverage;
PP2
Missense variant in the STAT1 gene, where missense mutations are typically associated with disease (based on misZ statistic). The gene has 64 curated pathogenic missense variants (we use a threshold of 10). The gene has 19 curated benign missense variants. Gene score misZ: 5.1492 (above the threshold of 3.09). Trascript score misZ: 7.0181 (above the threshold of 3.09). GenCC associations: The gene is linked to Mendelian susceptibility to mycobacterial diseases due to partial STAT1 deficiency, autoimmune enteropathy and endocrinopathy - susceptibility to chronic infections syndrome, immunodeficiency 31B.
BP4
Computational evidence support a benign effect (MetaRNN=0.14580896).
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
31
GnomAD4 exome Cov.: 31
GnomAD4 exome
Cov.:
31
GnomAD4 genome
GnomAD4 genome
Cov.:
31
ClinVar
Not reported inComputational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
DEOGEN2
Uncertain
D;D;.;.
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
N
LIST_S2
Uncertain
.;D;D;D
M_CAP
Benign
T
MetaRNN
Benign
T;T;T;T
MetaSVM
Benign
T
MutationAssessor
Benign
N;N;N;.
PrimateAI
Benign
T
PROVEAN
Benign
N;N;N;N
REVEL
Benign
Sift
Benign
T;T;T;T
Sift4G
Benign
T;T;T;T
Polyphen
B;B;B;.
Vest4
MutPred
Loss of catalytic residue at L270 (P = 0.0756);Loss of catalytic residue at L270 (P = 0.0756);Loss of catalytic residue at L270 (P = 0.0756);.;
MVP
MPC
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
No publications associated with this variant yet.