9-117713145-C-A
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_138554.5(TLR4):c.1017C>A(p.Asn339Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000342 in 1,461,074 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. N339D) has been classified as Uncertain significance.
Frequency
Consequence
NM_138554.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TLR4 | NM_138554.5 | c.1017C>A | p.Asn339Lys | missense_variant | 3/3 | ENST00000355622.8 | |
TLR4 | NM_003266.4 | c.897C>A | p.Asn299Lys | missense_variant | 4/4 | ||
TLR4 | NM_138557.3 | c.417C>A | p.Asn139Lys | missense_variant | 2/2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TLR4 | ENST00000355622.8 | c.1017C>A | p.Asn339Lys | missense_variant | 3/3 | 1 | NM_138554.5 | P1 | |
TLR4 | ENST00000394487.5 | c.897C>A | p.Asn299Lys | missense_variant | 4/4 | 1 | |||
TLR4 | ENST00000472304.2 | c.*751C>A | 3_prime_UTR_variant | 2/2 | 1 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 exomes AF: 0.00000800 AC: 2AN: 249926Hom.: 0 AF XY: 0.00000740 AC XY: 1AN XY: 135186
GnomAD4 exome AF: 0.00000342 AC: 5AN: 1461074Hom.: 0 Cov.: 32 AF XY: 0.00000413 AC XY: 3AN XY: 726730
GnomAD4 genome ? Cov.: 32
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Oct 07, 2022 | The c.1017C>A (p.N339K) alteration is located in exon 3 (coding exon 3) of the TLR4 gene. This alteration results from a C to A substitution at nucleotide position 1017, causing the asparagine (N) at amino acid position 339 to be replaced by a lysine (K). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at