rs41308230

Variant summary

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

The ENST00000360658.3(TLR9):​c.1200G>T​(p.Met400Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000656 in 152,374 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)

Consequence

TLR9
ENST00000360658.3 missense

Scores

1
3
15

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.281
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=0.17434019).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
TLR9NM_017442.4 linkuse as main transcriptc.1200G>T p.Met400Ile missense_variant 2/2 ENST00000360658.3 NP_059138.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
TLR9ENST00000360658.3 linkuse as main transcriptc.1200G>T p.Met400Ile missense_variant 2/21 NM_017442.4 ENSP00000353874 P1Q9NR96-1

Frequencies

GnomAD3 genomes
AF:
0.00000657
AC:
1
AN:
152256
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
Cov.:
36
GnomAD4 genome
AF:
0.00000656
AC:
1
AN:
152374
Hom.:
0
Cov.:
33
AF XY:
0.00
AC XY:
0
AN XY:
74518
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

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.77
BayesDel_addAF
Benign
-0.13
T
BayesDel_noAF
Benign
-0.43
CADD
Benign
19
DANN
Uncertain
0.99
DEOGEN2
Benign
0.14
T
Eigen
Benign
-0.40
Eigen_PC
Benign
-0.32
FATHMM_MKL
Benign
0.098
N
LIST_S2
Uncertain
0.90
D
M_CAP
Benign
0.011
T
MetaRNN
Benign
0.17
T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
0.53
N
MutationTaster
Benign
1.0
D
PrimateAI
Benign
0.46
T
PROVEAN
Benign
-1.9
N
REVEL
Benign
0.11
Sift
Uncertain
0.0090
D
Sift4G
Benign
0.33
T
Polyphen
0.21
B
Vest4
0.34
MutPred
0.47
Loss of MoRF binding (P = 0.1981);
MVP
0.61
MPC
0.56
ClinPred
0.42
T
GERP RS
4.1
Varity_R
0.26
gMVP
0.78

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: rs41308230; hg19: chr3-52257132; API