X-12919052-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_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
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• 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]

TLR8-AS1 (HGNC:):

ACMG classification

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

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 23

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

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: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.20
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.48
Cadd	Benign	21
Dann	Uncertain	0.99
DEOGEN2	Benign	0.22	T;.
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Benign	0.71	T;T
M_CAP	Uncertain	0.17	D
MetaRNN	Benign	0.25	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.2	M;.
MutationTaster	Benign	0.88	D;D
PrimateAI	Benign	0.37	T
PROVEAN	Benign	-1.4	N;N
REVEL	Benign	0.11
Sift	Pathogenic	0.0	D;D
Sift4G	Benign	0.21	T;T
Polyphen		0.69	P;.
Vest4		0.62
MutPred		0.54		Gain of sheet (P = 0.0061);.;
MVP		0.28
MPC		1.7
ClinPred		0.94	D
GERP RS		5.3
Varity_R		0.93
gMVP		0.59

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: chrX-12937171;