chrX-12919052-G-T
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_138636.5(TLR8):c.12G>T(p.Met4Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: not found (cov: 23)
Consequence
TLR8
NM_138636.5 missense
NM_138636.5 missense
Scores
1
4
12
Clinical Significance
Conservation
PhyloP100: 2.92
Genes affected
TLR8 (HGNC:15632): (toll like receptor 8) 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. The various TLRs exhibit different patterns of expression. This gene is predominantly expressed in lung and peripheral blood leukocytes, and lies in close proximity to another family member, TLR7, on chromosome X. [provided by RefSeq, Jul 2008]
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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=0.25084767).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TLR8 | NM_138636.5 | c.12G>T | p.Met4Ile | missense_variant | 2/2 | ENST00000218032.7 | |
TLR8-AS1 | NR_030727.1 | n.241-10719C>A | intron_variant, non_coding_transcript_variant | ||||
TLR8 | NM_016610.4 | c.66G>T | p.Met22Ile | missense_variant | 3/3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TLR8 | ENST00000218032.7 | c.12G>T | p.Met4Ile | missense_variant | 2/2 | 1 | NM_138636.5 | P2 | |
TLR8 | ENST00000311912.5 | c.66G>T | p.Met22Ile | missense_variant | 3/3 | 1 | A2 |
Frequencies
GnomAD3 genomes ? Cov.: 23
GnomAD3 genomes
?
Cov.:
23
GnomAD4 exome Cov.: 30
GnomAD4 exome
Cov.:
30
GnomAD4 genome ? Cov.: 23
GnomAD4 genome
?
Cov.:
23
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Mar 01, 2024 | TLR8: PM2, BP4 - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Benign
Dann
Uncertain
DEOGEN2
Benign
T;.
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
T;T
M_CAP
Uncertain
D
MetaRNN
Benign
T;T
MetaSVM
Benign
T
MutationAssessor
Uncertain
M;.
MutationTaster
Benign
D;D
PrimateAI
Benign
T
PROVEAN
Benign
N;N
REVEL
Benign
Sift
Pathogenic
D;D
Sift4G
Benign
T;T
Polyphen
P;.
Vest4
MutPred
Gain of sheet (P = 0.0061);.;
MVP
MPC
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
No publications associated with this variant yet.