Variant X-12920212-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong

The NM_138636.5(TLR8):c.1172T>C(p.Met391Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000654 in 1,207,843 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 25 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000036 ( 0 hom., 0 hem., cov: 23)

Exomes 𝑓: 0.000068 ( 0 hom. 25 hem. )

Consequence

TLR8
NM_138636.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.224

Variant links:

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 links:

TLR8-AS1 (HGNC:):

TLR8-AS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.060513884).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
TLR8	NM_138636.5 linkuse as main transcript	c.1172T>C	p.Met391Thr	missense_variant	2/2	ENST00000218032.7
TLR8-AS1	NR_030727.1 linkuse as main transcript	n.241-11879A>G		intron_variant, non_coding_transcript_variant
TLR8	NM_016610.4 linkuse as main transcript	c.1226T>C	p.Met409Thr	missense_variant	3/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TLR8	ENST00000218032.7 linkuse as main transcript	c.1172T>C	p.Met391Thr	missense_variant	2/2	1	NM_138636.5	P2	Q9NR97-1
TLR8	ENST00000311912.5 linkuse as main transcript	c.1226T>C	p.Met409Thr	missense_variant	3/3	1		A2	Q9NR97-2

Frequencies

GnomAD3 genomes

AF:

0.0000357

AC:

AN:

112176

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

34316

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:

0.0000751

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000166

AC:

AN:

180743

Hom.:

AF XY:

0.0000152

AC XY:

AN XY:

65639

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000371

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000247

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000685

AC:

AN:

1095667

Hom.:

Cov.:

AF XY:

0.0000692

AC XY:

AN XY:

361225

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000287

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000741

Gnomad4 NFE exome

AF:

0.0000773

Gnomad4 OTH exome

AF:

0.000130

GnomAD4 genome

AF:

0.0000357

AC:

AN:

112176

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

34316

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:

0.0000751

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000712

Hom.:

Bravo

AF:

0.0000151

ExAC

AF:

0.00000824

AC:

EpiCase

AF:

0.000164

EpiControl

AF:

0.0000593

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

May 01, 2022

TLR8: PM2, BP4 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.23

BayesDel_addAF

Benign

-0.50

BayesDel_noAF

Benign

-0.85

Cadd

Benign

1.1

Dann

Benign

0.25

DEOGEN2

Benign

0.12

T;.

FATHMM_MKL

Benign

0.15

LIST_S2

Benign

0.59

T;T

M_CAP

Benign

0.014

MetaRNN

Benign

0.061

T;T

MetaSVM

Benign

-0.93

MutationAssessor

Benign

1.0

L;.

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.29

PROVEAN

Benign

-1.1

N;N

REVEL

Benign

0.013

Sift

Benign

0.40

T;T

Sift4G

Benign

0.39

T;T

Polyphen

0.0030

B;.

Vest4

0.12

MutPred

0.38

Gain of glycosylation at M391 (P = 0.0621);.;

MVP

0.11

MPC

0.86

ClinPred

0.022

GERP RS

-1.2

Varity_R

0.33

gMVP

0.49

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over