NM_006068.5:c.1775G>A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_006068.5(TLR6):​c.1775G>A​(p.Gly592Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,702 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G592V) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

TLR6
NM_006068.5 missense

Scores

1
4
14

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.525
Variant links:
Genes affected
TLR6 (HGNC:16711): (toll like receptor 6) 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 receptor functionally interacts with toll-like receptor 2 to mediate cellular response to bacterial lipoproteins. A Ser249Pro polymorphism in the extracellular domain of the encoded protein may be associated with an increased of asthma is some populations.[provided by RefSeq, Jan 2011]
TLR1 (HGNC:11847): (toll like receptor 1) 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 ubiquitously expressed, and at higher levels than other TLR genes. Different length transcripts presumably resulting from use of alternative polyadenylation site, and/or from alternative splicing, have been noted for this gene. [provided by RefSeq, Jul 2008]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.4163298).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
TLR6NM_006068.5 linkc.1775G>A p.Gly592Asp missense_variant Exon 2 of 2 ENST00000508254.6 NP_006059.2 Q9Y2C9-1B2R933

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
TLR6ENST00000508254.6 linkc.1775G>A p.Gly592Asp missense_variant Exon 2 of 2 1 NM_006068.5 ENSP00000424718.2 Q9Y2C9-1D6RAV7
TLR6ENST00000381950.2 linkc.1775G>A p.Gly592Asp missense_variant Exon 3 of 3 6 ENSP00000371376.1 Q9Y2C9-1
TLR1ENST00000506146.5 linkc.-352-22506G>A intron_variant Intron 1 of 5 4 ENSP00000423725.1 D6RCE8

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
6.84e-7
AC:
1
AN:
1461702
Hom.:
0
Cov.:
36
AF XY:
0.00000138
AC XY:
1
AN XY:
727174
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:
8.99e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.68
BayesDel_addAF
Benign
-0.16
T
BayesDel_noAF
Benign
-0.46
CADD
Benign
6.1
DANN
Benign
0.84
DEOGEN2
Benign
0.076
T;T
Eigen
Benign
-0.95
Eigen_PC
Benign
-1.1
FATHMM_MKL
Benign
0.27
N
LIST_S2
Uncertain
0.94
D;.
M_CAP
Benign
0.0065
T
MetaRNN
Benign
0.42
T;T
MetaSVM
Benign
-0.99
T
MutationAssessor
Uncertain
2.8
M;M
PrimateAI
Benign
0.28
T
PROVEAN
Benign
-1.5
N;N
REVEL
Benign
0.13
Sift
Uncertain
0.012
D;D
Sift4G
Uncertain
0.056
T;T
Polyphen
0.45
P;P
Vest4
0.43
MutPred
0.67
Loss of glycosylation at T590 (P = 0.0368);Loss of glycosylation at T590 (P = 0.0368);
MVP
0.31
MPC
0.38
ClinPred
0.45
T
GERP RS
-4.9
Varity_R
0.10
gMVP
0.66

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr4-38829320; API