Genetic Variant TLR6:p.Ser249Ala (chr4-38828727-TGA-GGC) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is The variant received 2 classification points (ACGS-UK Somatic Oncogenicity v2025). O3_Moderate

The NM_006068.5(TLR6):c.745_747delTCAinsGCC (p.Ser249Ala) variant causes a missense change. Note: allele frequency estimates from gnomAD may be inaccurate for this variant type (MNP or indel longer than 3 bp) due to technology limitations. The variant is absent from the gnomAD population database at sites with sufficient sequencing coverage. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Other variants at the same amino acid position have been reported in ClinVar (not pathogenic): p.S249A: protective (ClinVar VariationId 1710535, 0 stars)

Frequency

Genomes: not found (cov: 32)

Consequence

TLR6
NM_006068.5 missense

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.84

Publications

0 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

new If you want to explore the variant's impact on the transcript NM_006068.5, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

Classification according to ACGS-UK Somatic Oncogenicity v2025

Classification was made for transcript:

Our verdict: Uncertain_significance. The variant received 2 points.

Show applied only (1)

Apply	Criterion Code & Title / Strength	Strength	Rationale / Clinical Context
	O3Absent or very rare in population		Absent or extremely rare in gnomAD (AC ≤ 2) — O3 moderate; GnomAD: AF = absent, AC = 0 — absent/extremely rare (O3 moderate [+2])

Variant Effect in Transcripts

Automated classification analysis was done for transcript: NM_006068.5. You can select a different transcript below to see updated classification assignments.

RefSeq Transcripts

Sel.	Gene / Transcript	Tags	HGVSc / HGVSp	Effect	Exon rank	Protein / UniProt
	TLR6 NM_006068.5	MANE Select	c.745_747delTCAinsGCC p.Ser249Ala	missense	N/A	Prot: NP_006059.2
	TLR6 NM_001394553.1		c.745_747delTCAinsGCC p.Ser249Ala	missense	N/A	Prot: NP_001381482.1 UniProt: Q9Y2C9-1

TLR6 NM_006068.5

MANE Select

HGVSc / HGVSpc.745_747delTCAinsGCCp.Ser249Ala

Exon rankN/A

missense

Prot: NP_006059.2

TLR6 NM_001394553.1

HGVSc / HGVSpc.745_747delTCAinsGCCp.Ser249Ala

Exon rankN/A

missense

Prot: NP_001381482.1UniProt: Q9Y2C9-1

Ensembl Transcripts

Gene / Transcript	Tags	HGVSc / HGVSp	Effect	Exon rank	Protein / UniProt
TLR6 ENST00000508254.6	TSL:1MANE Select	c.745_747delTCAinsGCC p.Ser249Ala	missense	N/A	Prot: ENSP00000424718.2 UniProt: Q9Y2C9-1
TLR6 ENST00000381950.2	TSL:6	c.745_747delTCAinsGCC p.Ser249Ala	missense	N/A	Prot: ENSP00000371376.1 UniProt: Q9Y2C9-1
TLR6 ENST00000966018.1		c.745_747delTCAinsGCC p.Ser249Ala	missense	N/A	Prot: ENSP00000636077.1 UniProt: Q9Y2C9-1

TLR6 ENST00000508254.6

TSL:1MANE Select

HGVSc / HGVSpc.745_747delTCAinsGCCp.Ser249Ala

Exon rankN/A

missense

Prot: ENSP00000424718.2UniProt: Q9Y2C9-1

TLR6 ENST00000381950.2

TSL:6

HGVSc / HGVSpc.745_747delTCAinsGCCp.Ser249Ala

Exon rankN/A

missense

Prot: ENSP00000371376.1UniProt: Q9Y2C9-1

TLR6 ENST00000966018.1

HGVSc / HGVSpc.745_747delTCAinsGCCp.Ser249Ala

Exon rankN/A

missense

Prot: ENSP00000636077.1UniProt: Q9Y2C9-1

Frequencies

Allele frequencies (AF), counts (AC/AN), homozygotes and coverage

Common (AF > 0.05 / Hom > 5)

Rare (AF ≤ 0.0001 / Hom ≤ 1)

Source / population	AF	AC	Hom	AN	Coverage
Global population databases 2 sources Large-scale international reference populations
GnomAD3 genomes	AF:	AC:	Hom:	AN:	Cov:32
GnomAD4 genome	AF:	AC:	Hom:	AN:	Cov:32

Showing 2 sources

Tested, but no data found:GnomAD4 exomeIf GnomAD4 is missing, the position is probably not covered by the project.

ClinVar

Not reported in ClinVar

Computational Scores

Algorithm	Calibrated pred.	Score	Prediction
PhyloP100	Benign	1.8

Showing 1 of 1 scores

Splicing Scores

No splicing scores have been computed for this variant.

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

MaveDB functional evidence

MaveDB is a public repository of laboratory assays that test the effect of thousands of variants at once — treat this as supporting research data and interpret it with great caution; it is not a clinical classification.

No MaveDB functional evidence found for this variant.

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

Classification according to ACGS-UK Somatic Oncogenicity v2025

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational Scores

Splicing Scores

MaveDB functional evidence ?

Publications

Other links and lift over

MaveDB functional evidence