Variant X-12919236-A-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -1 ACMG points: 0P and 1B. BP4

The NM_138636.5(TLR8):c.196A>T(p.Thr66Ser) variant causes a missense change. The variant allele was found at a frequency of 0.0000392 in 1,098,060 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 16 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T66A) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 23)

Exomes 𝑓: 0.000039 ( 0 hom. 16 hem. )

Consequence

TLR8
NM_138636.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.91

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 -1 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.34349835).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
TLR8	NM_138636.5 linkuse as main transcript	c.196A>T	p.Thr66Ser	missense_variant	2/2	ENST00000218032.7
TLR8-AS1	NR_030727.1 linkuse as main transcript	n.241-10903T>A		intron_variant, non_coding_transcript_variant
TLR8	NM_016610.4 linkuse as main transcript	c.250A>T	p.Thr84Ser	missense_variant	3/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TLR8	ENST00000218032.7 linkuse as main transcript	c.196A>T	p.Thr66Ser	missense_variant	2/2	1	NM_138636.5	P2	Q9NR97-1
TLR8	ENST00000311912.5 linkuse as main transcript	c.250A>T	p.Thr84Ser	missense_variant	3/3	1		A2	Q9NR97-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000546

AC:

AN:

183037

Hom.:

AF XY:

0.00

AC XY:

AN XY:

67613

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

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:

0.0000123

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000392

AC:

AN:

1098060

Hom.:

Cov.:

AF XY:

0.0000440

AC XY:

AN XY:

363416

show subpopulations

Gnomad4 AFR exome

AF:

0.00

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:

0.0000511

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

EpiCase

AF:

0.000218

EpiControl

AF:

0.0000593

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 submitter

clinical testing

Ambry Genetics

Nov 08, 2022

The c.196A>T (p.T66S) alteration is located in exon 2 (coding exon 2) of the TLR8 gene. This alteration results from a A to T substitution at nucleotide position 196, causing the threonine (T) at amino acid position 66 to be replaced by a serine (S). 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

0.24

BayesDel_addAF

Benign

-0.14

BayesDel_noAF

Benign

-0.44

Cadd

Benign

Dann

Uncertain

0.99

DEOGEN2

Benign

0.33

T;.

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Benign

0.79

T;T

M_CAP

Uncertain

0.088

MetaRNN

Benign

0.34

T;T

MetaSVM

Benign

-0.53

MutationAssessor

Uncertain

2.0

M;.

MutationTaster

Benign

0.99

D;D

PrimateAI

Benign

0.44

PROVEAN

Uncertain

-3.4

D;D

REVEL

Uncertain

0.31

Sift

Uncertain

0.0040

D;D

Sift4G

Uncertain

0.012

D;D

Polyphen

1.0

D;.

Vest4

0.36

MutPred

0.46

Gain of ubiquitination at K63 (P = 0.0619);.;

MVP

0.72

MPC

1.7

ClinPred

0.78

GERP RS

4.0

Varity_R

0.62

gMVP

0.55

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