3-52221285-T-C

Variant summary

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

The NM_017442.4(TLR9):ā€‹c.3031A>Gā€‹(p.Met1011Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000655 in 1,526,986 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 (ā˜…).

Frequency

Genomes: š‘“ 0.0000066 ( 0 hom., cov: 33)
Exomes š‘“: 0.0000065 ( 0 hom. )

Consequence

TLR9
NM_017442.4 missense

Scores

19

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.0170
Variant links:
Genes affected
TLR9 (HGNC:15633): (toll like receptor 9) The protein encoded by this gene is a member of the Toll-like receptor (TLR) family, which plays a fundamental role in pathogen recognition and activation of innate immunity. TLRs are highly conserved from Drosophila to humans and share structural and functional similarities. They recognize pathogen-associated molecular patterns (PAMPs) that are expressed on infectious agents, and mediate the production of cytokines necessary for the development of effective immunity. Studies in mice and human indicate that this receptor mediates cellular response to unmethylated CpG dinucleotides in bacterial DNA to mount an innate immune response. [provided by RefSeq, Aug 2017]

Genome browser will be placed here

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=0.0762234).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
TLR9NM_017442.4 linkuse as main transcriptc.3031A>G p.Met1011Val missense_variant 2/2 ENST00000360658.3 NP_059138.1 Q9NR96-1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
TLR9ENST00000360658.3 linkuse as main transcriptc.3031A>G p.Met1011Val missense_variant 2/21 NM_017442.4 ENSP00000353874.2 Q9NR96-1
ENSG00000173366ENST00000494383.1 linkuse as main transcriptc.3490A>G p.Met1164Val missense_variant 5/52 ENSP00000417517.1 H0Y858

Frequencies

GnomAD3 genomes
AF:
0.00000657
AC:
1
AN:
152214
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000147
Gnomad OTH
AF:
0.00
GnomAD4 exome
AF:
0.00000655
AC:
9
AN:
1374772
Hom.:
0
Cov.:
30
AF XY:
0.00000889
AC XY:
6
AN XY:
674614
show subpopulations
Gnomad4 AFR exome
AF:
0.0000328
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:
0.00000747
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.00000657
AC:
1
AN:
152214
Hom.:
0
Cov.:
33
AF XY:
0.00
AC XY:
0
AN XY:
74370
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000147
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.00000378

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsDec 28, 2022The c.3031A>G (p.M1011V) alteration is located in exon 2 (coding exon 2) of the TLR9 gene. This alteration results from a A to G substitution at nucleotide position 3031, causing the methionine (M) at amino acid position 1011 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.073
BayesDel_addAF
Benign
-0.28
T
BayesDel_noAF
Benign
-0.63
CADD
Benign
3.0
DANN
Benign
0.64
DEOGEN2
Benign
0.068
T
Eigen
Benign
-0.91
Eigen_PC
Benign
-0.88
FATHMM_MKL
Benign
0.081
N
LIST_S2
Benign
0.56
T
M_CAP
Benign
0.0074
T
MetaRNN
Benign
0.076
T
MetaSVM
Benign
-0.88
T
MutationAssessor
Benign
0.0
N
PrimateAI
Benign
0.28
T
PROVEAN
Benign
-0.38
N
REVEL
Benign
0.037
Sift
Benign
0.55
T
Sift4G
Benign
0.12
T
Polyphen
0.0
B
Vest4
0.044
MutPred
0.47
Loss of MoRF binding (P = 0.1092);
MVP
0.35
MPC
0.47
ClinPred
0.011
T
GERP RS
1.4
Varity_R
0.028
gMVP
0.48

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs199839624; hg19: chr3-52255301; API