2-191031497-C-G
Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 1P and 4B. PP2BS2
The NM_003151.4(STAT4):c.2064G>C(p.Arg688Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000558 in 1,613,002 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/23 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R688G) has been classified as Uncertain significance.
Frequency
Consequence
NM_003151.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
STAT4 | NM_003151.4 | c.2064G>C | p.Arg688Ser | missense_variant | 22/24 | ENST00000392320.7 | |
STAT4-AS1 | NR_136318.1 | n.243+400C>G | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
STAT4 | ENST00000392320.7 | c.2064G>C | p.Arg688Ser | missense_variant | 22/24 | 1 | NM_003151.4 | P1 | |
STAT4-AS1 | ENST00000456176.5 | n.243+400C>G | intron_variant, non_coding_transcript_variant | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.00000657 AC: 1AN: 152110Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000319 AC: 8AN: 250982Hom.: 0 AF XY: 0.0000295 AC XY: 4AN XY: 135660
GnomAD4 exome AF: 0.00000548 AC: 8AN: 1460892Hom.: 0 Cov.: 31 AF XY: 0.00000688 AC XY: 5AN XY: 726708
GnomAD4 genome ? AF: 0.00000657 AC: 1AN: 152110Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74302
ClinVar
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Feb 20, 2022 | Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0"). 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. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. This variant has not been reported in the literature in individuals affected with STAT4-related conditions. This variant is present in population databases (rs768045385, gnomAD 0.05%). This sequence change replaces arginine, which is basic and polar, with serine, which is neutral and polar, at codon 688 of the STAT4 protein (p.Arg688Ser). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at