rs863223364

Variant names:

• chr4-38827743-CAT-C
• rs863223364
• NM_006068.5:c.1729_1730delAT

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP6

The NM_006068.5(TLR6):​c.1729_1730delAT​(p.Met577ValfsTer2) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Benign (no stars).

• Frequency: Genomes: not found (cov: 32)
• Consequence: TLR6 NM_006068.5 frameshift
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: 3.58
• Publications: 1 publications found

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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP6: Variant 4-38827743-CAT-C is Benign according to our data. Variant chr4-38827743-CAT-C is described in ClinVar as Benign. ClinVar VariationId is 208867.Status of the report is no_assertion_criteria_provided, 0 stars.

Variant Effect in Transcripts

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

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TLR6	NM_006068.5	MANE Select	c.1729_1730delAT	p.Met577ValfsTer2	frameshift	Exon 2 of 2	NP_006059.2
	TLR6	NM_001394553.1		c.1729_1730delAT	p.Met577ValfsTer2	frameshift	Exon 2 of 2	NP_001381482.1	Q9Y2C9-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TLR6	ENST00000508254.6	TSL:1 MANE Select	c.1729_1730delAT	p.Met577ValfsTer2	frameshift	Exon 2 of 2	ENSP00000424718.2	Q9Y2C9-1
	TLR6	ENST00000381950.2	TSL:6	c.1729_1730delAT	p.Met577ValfsTer2	frameshift	Exon 3 of 3	ENSP00000371376.1	Q9Y2C9-1
	TLR6	ENST00000966018.1		c.1729_1730delAT	p.Met577ValfsTer2	frameshift	Exon 2 of 2	ENSP00000636077.1

Frequencies

GnomAD3 genomes Cov.: 32

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	Abnormality of neuronal migration (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		3.6

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

Other links and lift over

dbSNP: rs863223364; hg19: chr4-38829364;