rs199795457
Variant summary
Our verdict is Benign. Variant got -7 ACMG points: 0P and 7B. BP4_ModerateBS1_SupportingBS2
The NM_198282.4(STING1):c.757C>T(p.Arg253Trp) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000658 in 1,611,182 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. 2/3 splice prediction tools predict no significant impact on normal splicing. 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. R253Q) has been classified as Likely benign.
Frequency
Consequence
NM_198282.4 missense, splice_region
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -7 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
STING1 | NM_198282.4 | c.757C>T | p.Arg253Trp | missense_variant, splice_region_variant | 6/8 | ENST00000330794.9 | |
STING1 | NM_001301738.2 | c.757C>T | p.Arg253Trp | missense_variant, splice_region_variant | 6/7 | ||
STING1 | NM_001367258.1 | c.400C>T | p.Arg134Trp | missense_variant, splice_region_variant | 5/7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
STING1 | ENST00000330794.9 | c.757C>T | p.Arg253Trp | missense_variant, splice_region_variant | 6/8 | 1 | NM_198282.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000657 AC: 10AN: 152092Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000638 AC: 16AN: 250616Hom.: 0 AF XY: 0.0000664 AC XY: 9AN XY: 135506
GnomAD4 exome AF: 0.0000658 AC: 96AN: 1458972Hom.: 0 Cov.: 29 AF XY: 0.0000703 AC XY: 51AN XY: 725652
GnomAD4 genome ? AF: 0.0000657 AC: 10AN: 152210Hom.: 0 Cov.: 32 AF XY: 0.0000672 AC XY: 5AN XY: 74422
ClinVar
Submissions by phenotype
STING-associated vasculopathy with onset in infancy Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Mar 24, 2023 | Experimental studies have shown that this missense change affects TMEM173 function (PMID: 29367762). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. ClinVar contains an entry for this variant (Variation ID: 541978). This variant has not been reported in the literature in individuals affected with TMEM173-related conditions. This variant is present in population databases (rs199795457, gnomAD 0.02%). This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 253 of the TMEM173 protein (p.Arg253Trp). 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. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at