rs201015563
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_198282.4(STING1):c.979C>A(p.Gln327Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,210 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/20 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. Q327P) has been classified as Uncertain significance.
Frequency
Consequence
NM_198282.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
STING1 | NM_198282.4 | c.979C>A | p.Gln327Lys | missense_variant | 8/8 | ENST00000330794.9 | |
STING1 | NM_001367258.1 | c.622C>A | p.Gln208Lys | missense_variant | 7/7 | ||
STING1 | NM_001301738.2 | c.792C>A | p.Pro264= | synonymous_variant | 7/7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
STING1 | ENST00000330794.9 | c.979C>A | p.Gln327Lys | missense_variant | 8/8 | 1 | NM_198282.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00000657 AC: 1AN: 152092Hom.: 0 Cov.: 31
GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251228Hom.: 0 AF XY: 0.00000737 AC XY: 1AN XY: 135768
GnomAD4 exome Cov.: 31
GnomAD4 genome ? AF: 0.00000657 AC: 1AN: 152210Hom.: 0 Cov.: 31 AF XY: 0.0000134 AC XY: 1AN XY: 74418
ClinVar
Submissions by phenotype
STING-associated vasculopathy with onset in infancy Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Mar 06, 2020 | 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 missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The lysine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. These predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has not been reported in the literature in individuals with TMEM173-related disease. This variant is present in population databases (rs201015563, ExAC 0.01%). This sequence change replaces glutamine with lysine at codon 327 of the TMEM173 protein (p.Gln327Lys). The glutamine residue is moderately conserved and there is a small physicochemical difference between glutamine and lysine. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at