NM_006068.5:c.979G>A

Variant names:

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_006068.5(TLR6):c.979G>A(p.Val327Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00663 in 1,614,054 control chromosomes in the GnomAD database, including 214 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.013 ( 45 hom., cov: 33)

Exomes 𝑓: 0.0059 ( 169 hom. )

Consequence

TLR6
NM_006068.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.219

Publications

22 publications found

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]

TLR6 links:

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]

TLR1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.002669394).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0662 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TLR6	NM_006068.5 link	c.979G>A	p.Val327Met	missense_variant	Exon 2 of 2	ENST00000508254.6	NP_006059.2	Q9Y2C9-1B2R933

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
TLR6	ENST00000508254.6 link	c.979G>A	p.Val327Met	missense_variant	Exon 2 of 2	1	NM_006068.5	ENSP00000424718.2	Q9Y2C9-1D6RAV7
TLR6	ENST00000381950.2 link	c.979G>A	p.Val327Met	missense_variant	Exon 3 of 3	6		ENSP00000371376.1	Q9Y2C9-1
TLR1	ENST00000506146.5 link	c.-352-23302G>A		intron_variant	Intron 1 of 5	4		ENSP00000423725.1	D6RCE8

Frequencies

GnomAD3 genomes

AF:

0.0133

AC:

2031

AN:

152162

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0283

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.00700

Gnomad ASJ

AF:

0.00691

Gnomad EAS

AF:

0.0721

Gnomad SAS

AF:

0.0267

Gnomad FIN

AF:

0.00434

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.00215

Gnomad OTH

AF:

0.0139

GnomAD2 exomes

AF:

0.0121

AC:

3042

AN:

251140

AF XY:

0.0122

show subpopulations

Gnomad AFR exome

AF:

0.0281

Gnomad AMR exome

AF:

0.00321

Gnomad ASJ exome

AF:

0.00645

Gnomad EAS exome

AF:

0.0721

Gnomad FIN exome

AF:

0.00342

Gnomad NFE exome

AF:

0.00264

Gnomad OTH exome

AF:

0.00833

GnomAD4 exome

AF:

0.00593

AC:

8671

AN:

1461774

Hom.:

169

Cov.:

AF XY:

0.00644

AC XY:

4685

AN XY:

727184

show subpopulations

African (AFR)

AF:

0.0265

AC:

888

AN:

33478

American (AMR)

AF:

0.00326

AC:

146

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00559

AC:

146

AN:

26130

East Asian (EAS)

AF:

0.0618

AC:

2452

AN:

39682

South Asian (SAS)

AF:

0.0230

AC:

1985

AN:

86246

European-Finnish (FIN)

AF:

0.00309

AC:

165

AN:

53414

Middle Eastern (MID)

AF:

0.0115

AC:

AN:

5758

European-Non Finnish (NFE)

AF:

0.00185

AC:

2056

AN:

1111954

Other (OTH)

AF:

0.0127

AC:

767

AN:

60388

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.465

Heterozygous variant carriers

501

1002

1504

2005

2506

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

140

280

420

560

700

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0134

AC:

2036

AN:

152280

Hom.:

Cov.:

AF XY:

0.0135

AC XY:

1003

AN XY:

74462

show subpopulations

African (AFR)

AF:

0.0282

AC:

1170

AN:

41550

American (AMR)

AF:

0.00700

AC:

107

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.00691

AC:

AN:

3472

East Asian (EAS)

AF:

0.0722

AC:

375

AN:

5192

South Asian (SAS)

AF:

0.0267

AC:

129

AN:

4826

European-Finnish (FIN)

AF:

0.00434

AC:

AN:

10602

Middle Eastern (MID)

AF:

0.0102

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00215

AC:

146

AN:

68026

Other (OTH)

AF:

0.0166

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

104

208

313

417

521

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

104

130

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00831

Hom.:

Bravo

AF:

0.0134

TwinsUK

AF:

0.00243

AC:

ALSPAC

AF:

0.00104

AC:

ESP6500AA

AF:

0.0277

AC:

122

ESP6500EA

AF:

0.00221

AC:

ExAC

AF:

0.0126

AC:

1531

Asia WGS

AF:

0.0680

AC:

238

AN:

3476

EpiCase

AF:

0.00251

EpiControl

AF:

0.00284

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.71

BayesDel_noAF

Benign

-0.73

CADD

Benign

9.7

(source)

DANN

Benign

0.96

DEOGEN2

Benign

0.058

T;T;.

Eigen

Benign

-0.66

Eigen_PC

Benign

-0.74

FATHMM_MKL

Benign

0.025

LIST_S2

Benign

0.12

T;.;T

MetaRNN

Benign

0.0027

T;T;T

MetaSVM

Benign

-0.97

MutationAssessor

Uncertain

2.7

M;M;M

PhyloP100

-0.22

PrimateAI

Benign

0.36

PROVEAN

Benign

-0.72

N;N;.

REVEL

Benign

0.049

Sift

Benign

0.099

T;T;.

Sift4G

Benign

0.13

T;T;T

Polyphen

0.30

B;B;.

Vest4

0.15

MPC

0.16

ClinPred

0.0068

GERP RS

0.62

Varity_R

0.024

gMVP

0.44

Mutation Taster

=99/1

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over