chr1-223110913-C-A

Variant names:

• chr1-223110913-C-A
• NM_003268.6:c.2119G>T

Variant summary

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

The NM_003268.6(TLR5):​c.2119G>T​(p.Val707Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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. V707M) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: TLR5 NM_003268.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.30

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TLR5	NM_003268.6	c.2119G>T	p.Val707Leu	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.2119G>T	p.Val707Leu	missense_variant	Exon 6 of 6		NM_003268.6	ENSP00000496355.1
TLR5	ENST00000540964.5	c.2119G>T	p.Val707Leu	missense_variant	Exon 4 of 4	5
TLR5	ENST00000645434.1	c.2119G>T	p.Val707Leu	missense_variant	Exon 5 of 5			ENSP00000493892.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.61
BayesDel_addAF	Benign	-0.025	T
BayesDel_noAF	Benign	-0.27
CADD	Uncertain	25
DANN	Uncertain	1.0
Eigen	Pathogenic	0.99
Eigen_PC	Pathogenic	0.92
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Pathogenic	0.98	D;.;.;D
M_CAP	Benign	0.069	D
MetaRNN	Uncertain	0.72	D;D;D;D
MetaSVM	Benign	-0.74	T
PrimateAI	Uncertain	0.51	T
PROVEAN	Benign	-2.0	N;.;N;.
REVEL	Uncertain	0.34
Sift	Uncertain	0.0030	D;.;D;.
Sift4G	Uncertain	0.013	D;.;D;.
Vest4		0.56
MutPred		0.63		Gain of ubiquitination at K702 (P = 0.1162);Gain of ubiquitination at K702 (P = 0.1162);Gain of ubiquitination at K702 (P = 0.1162);Gain of ubiquitination at K702 (P = 0.1162);
MVP		0.80
MPC		0.34
ClinPred		0.99	D
GERP RS		5.6
gMVP		0.68

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: chr1-223284255;