rs1178340807
Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2
The NM_015559.3(SETBP1):c.4046G>C(p.Ser1349Thr) variant causes a missense change. The variant allele was found at a frequency of 0.0000062 in 1,614,050 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 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. S1349N) has been classified as Uncertain significance.
Frequency
Consequence
NM_015559.3 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Likely_benign. Variant got -6 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SETBP1 | NM_015559.3 | c.4046G>C | p.Ser1349Thr | missense_variant | 5/6 | ENST00000649279.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SETBP1 | ENST00000649279.2 | c.4046G>C | p.Ser1349Thr | missense_variant | 5/6 | NM_015559.3 | P2 |
Frequencies
GnomAD3 genomes ? AF: 0.0000329 AC: 5AN: 152192Hom.: 0 Cov.: 32
GnomAD4 exome AF: 0.00000342 AC: 5AN: 1461858Hom.: 0 Cov.: 32 AF XY: 0.00000688 AC XY: 5AN XY: 727230
GnomAD4 genome ? AF: 0.0000329 AC: 5AN: 152192Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2AN XY: 74360
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Dec 27, 2017 | - - |
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Aug 16, 2016 | - - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Nov 29, 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) performed at Invitae indicates that this missense variant is not expected to disrupt SETBP1 protein function. ClinVar contains an entry for this variant (Variation ID: 521227). This variant has not been reported in the literature in individuals affected with SETBP1-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces serine, which is neutral and polar, with threonine, which is neutral and polar, at codon 1349 of the SETBP1 protein (p.Ser1349Thr). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at