NM_198282.4:c.1110G>T

Variant names:

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_198282.4(STING1):c.1110G>T(p.Lys370Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000138 in 1,450,544 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. K370K) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

STING1
NM_198282.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.264

Publications

0 publications found

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]

STING1 Gene-Disease associations (from GenCC):

STING-associated vasculopathy with onset in infancy
Inheritance: AD, AR Classification: STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Genomics England PanelApp, PanelApp Australia, Orphanet
familial chilblain lupus
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

STING1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.08794978).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_198282.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
STING1	NM_198282.4	MANE Select	c.1110G>T	p.Lys370Asn	missense	Exon 8 of 8	NP_938023.1	Q86WV6
STING1	NM_001367258.1		c.753G>T	p.Lys251Asn	missense	Exon 7 of 7	NP_001354187.1	A0A494C0W5
STING1	NM_001301738.2		c.*71G>T		3_prime_UTR	Exon 7 of 7	NP_001288667.1	J3QTB1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
STING1	ENST00000330794.9	TSL:1 MANE Select	c.1110G>T	p.Lys370Asn	missense	Exon 8 of 8	ENSP00000331288.4	Q86WV6
STING1	ENST00000512606.6	TSL:1	n.1346G>T		non_coding_transcript_exon	Exon 6 of 6
STING1	ENST00000651699.1		c.1110G>T	p.Lys370Asn	missense	Exon 7 of 7	ENSP00000499166.1	Q86WV6

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000138

AC:

AN:

1450544

Hom.:

Cov.:

AF XY:

0.00000139

AC XY:

AN XY:

720784

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.00

AC:

AN:

33292

American (AMR)

AF:

0.00

AC:

AN:

43012

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25936

East Asian (EAS)

AF:

0.00

AC:

AN:

39258

South Asian (SAS)

AF:

0.0000118

AC:

AN:

84530

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52874

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4566

European-Non Finnish (NFE)

AF:

9.03e-7

AC:

AN:

1107164

Other (OTH)

AF:

0.00

AC:

AN:

59912

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.0448430), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.350

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.16

BayesDel_addAF

Benign

-0.29

BayesDel_noAF

Benign

-0.65

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.038

Eigen

Benign

-0.32

Eigen_PC

Benign

-0.29

FATHMM_MKL

Benign

0.36

LIST_S2

Benign

0.73

M_CAP

Benign

0.016

MetaRNN

Benign

0.088

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.1

PhyloP100

0.26

PrimateAI

Benign

0.30

PROVEAN

Benign

-0.63

REVEL

Benign

0.036

Sift

Benign

0.096

Sift4G

Benign

0.13

Polyphen

0.59

Vest4

0.16

MutPred

0.16

Loss of ubiquitination at K370 (P = 0.0023)

MVP

0.32

MPC

0.68

ClinPred

0.27

GERP RS

3.3

Varity_R

0.33

Mutation Taster

=77/23

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over