rs3024933
Variant summary
Our verdict is Likely benign. Variant got -1 ACMG points: 3P and 4B. PP2PP3_ModerateBS2
The NM_003151.4(STAT4):c.1750C>T(p.Arg584Trp) variant causes a missense change. The variant allele was found at a frequency of 0.00000558 in 1,613,758 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.
Frequency
Consequence
NM_003151.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
STAT4 | NM_003151.4 | c.1750C>T | p.Arg584Trp | missense_variant | 20/24 | ENST00000392320.7 | NP_003142.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
STAT4 | ENST00000392320.7 | c.1750C>T | p.Arg584Trp | missense_variant | 20/24 | 1 | NM_003151.4 | ENSP00000376134.2 | ||
STAT4 | ENST00000358470.8 | c.1750C>T | p.Arg584Trp | missense_variant | 20/24 | 1 | ENSP00000351255.4 | |||
STAT4 | ENST00000463951.1 | n.16C>T | non_coding_transcript_exon_variant | 1/3 | 4 | |||||
STAT4 | ENST00000495849.5 | n.1818C>T | non_coding_transcript_exon_variant | 20/21 | 2 |
Frequencies
GnomAD3 genomes AF: 0.00000658 AC: 1AN: 152060Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000120 AC: 3AN: 250650Hom.: 0 AF XY: 0.00000738 AC XY: 1AN XY: 135582
GnomAD4 exome AF: 0.00000547 AC: 8AN: 1461580Hom.: 0 Cov.: 31 AF XY: 0.00000688 AC XY: 5AN XY: 727076
GnomAD4 genome AF: 0.00000657 AC: 1AN: 152178Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74406
ClinVar
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Nov 23, 2022 | 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. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on STAT4 protein function. This variant has not been reported in the literature in individuals affected with STAT4-related conditions. This variant is present in population databases (rs3024933, gnomAD 0.003%). This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 584 of the STAT4 protein (p.Arg584Trp). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at