rs5744174

Variant names:

• chr1-223111186-A-C
• NM_003268.6:c.1846T>G

Your query was ambiguous. Multiple possible variants found:

• chr1-223111186-A-C
• chr1-223111186-A-G
• chr1-223111186-A-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_003268.6(TLR5):​c.1846T>G​(p.Phe616Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/19 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. F616L) has been classified as Benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: TLR5 NM_003268.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.844

Genes affected

TLR5 (HGNC:11851): (toll like receptor 5) This gene encodes a member of the toll-like receptor (TLR) family, which plays a fundamental role in pathogen recognition and activation of innate immune responses. These receptors recognize distinct pathogen-associated molecular patterns that are expressed on infectious agents. The protein encoded by this gene recognizes bacterial flagellin, the principal component of bacterial flagella and a virulence factor. The activation of this receptor mobilizes the nuclear factor NF-kappaB, which in turn activates a host of inflammatory-related target genes. Mutations in this gene have been associated with both resistance and susceptibility to systemic lupus erythematosus, and susceptibility to Legionnaire disease.[provided by RefSeq, Dec 2009]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.10656771).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TLR5	NM_003268.6	c.1846T>G	p.Phe616Val	missense_variant	Exon 6 of 6	ENST00000642603.2	NP_003259.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TLR5	ENST00000642603.2	c.1846T>G	p.Phe616Val	missense_variant	Exon 6 of 6		NM_003268.6	ENSP00000496355.1
TLR5	ENST00000540964.5	c.1846T>G	p.Phe616Val	missense_variant	Exon 4 of 4	5
TLR5	ENST00000645434.1	c.1846T>G	p.Phe616Val	missense_variant	Exon 5 of 5			ENSP00000493892.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 61

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.083
BayesDel_addAF	Benign	-0.36	T
BayesDel_noAF	Benign	-0.75
CADD	Benign	0.54
DANN	Benign	0.74
Eigen	Benign	-1.8
Eigen_PC	Benign	-2.0
FATHMM_MKL	Benign	0.067	N
LIST_S2	Benign	0.60	T;.;.;T
M_CAP	Benign	0.018	T
MetaRNN	Benign	0.11	T;T;T;T
MetaSVM	Benign	-0.90	T
PrimateAI	Benign	0.32	T
PROVEAN	Benign	-1.5	N;.;N;.
REVEL	Benign	0.057
Sift	Uncertain	0.0080	D;.;D;.
Sift4G	Uncertain	0.039	D;.;D;.
Vest4		0.046
MutPred		0.43		Gain of glycosylation at S615 (P = 0.1778);Gain of glycosylation at S615 (P = 0.1778);Gain of glycosylation at S615 (P = 0.1778);Gain of glycosylation at S615 (P = 0.1778);
MVP		0.13
MPC		0.067
ClinPred		0.41	T
GERP RS		-11
gMVP		0.71

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: chr1-223284528;