5-139478334-T-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_198282.4(STING1):​c.695A>C​(p.His232Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,882 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 31)
Exomes š‘“: 6.8e-7 ( 0 hom. )

Consequence

STING1
NM_198282.4 missense

Scores

1
2
16

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.21
Variant links:
Genes affected
STING1 (HGNC:27962): (stimulator of interferon response cGAMP interactor 1) This gene encodes a five transmembrane protein that functions as a major regulator of the innate immune response to viral and bacterial infections. The encoded protein is a pattern recognition receptor that detects cytosolic nucleic acids and transmits signals that activate type I interferon responses. The encoded protein has also been shown to play a role in apoptotic signaling by associating with type II major histocompatibility complex. Mutations in this gene are the cause of infantile-onset STING-associated vasculopathy. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Sep 2014]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.22356865).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
STING1NM_198282.4 linkc.695A>C p.His232Pro missense_variant Exon 6 of 8 ENST00000330794.9 NP_938023.1 Q86WV6
STING1NM_001301738.2 linkc.695A>C p.His232Pro missense_variant Exon 6 of 7 NP_001288667.1 J3QTB1V5V0K2
STING1NM_001367258.1 linkc.338A>C p.His113Pro missense_variant Exon 5 of 7 NP_001354187.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
STING1ENST00000330794.9 linkc.695A>C p.His232Pro missense_variant Exon 6 of 8 1 NM_198282.4 ENSP00000331288.4 Q86WV6

Frequencies

GnomAD3 genomes
Cov.:
31
GnomAD4 exome
AF:
6.84e-7
AC:
1
AN:
1461882
Hom.:
0
Cov.:
62
AF XY:
0.00
AC XY:
0
AN XY:
727240
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
8.99e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.61
BayesDel_addAF
Benign
-0.15
T
BayesDel_noAF
Benign
-0.46
CADD
Benign
19
DANN
Benign
0.93
DEOGEN2
Benign
0.13
T;.
Eigen
Benign
-0.58
Eigen_PC
Benign
-0.40
FATHMM_MKL
Benign
0.69
D
LIST_S2
Benign
0.52
T;.
M_CAP
Benign
0.0097
T
MetaRNN
Benign
0.22
T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
0.0
N;.
PrimateAI
Benign
0.40
T
PROVEAN
Benign
-1.6
N;N
REVEL
Benign
0.17
Sift
Uncertain
0.0070
D;D
Sift4G
Uncertain
0.0060
D;D
Polyphen
0.0
B;.
Vest4
0.18
MutPred
0.41
Gain of loop (P = 0.0502);Gain of loop (P = 0.0502);
MVP
0.36
MPC
0.81
ClinPred
0.68
D
GERP RS
4.9
Varity_R
0.84

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr5-138857919; API