7-28955963-T-C
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Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4
The NM_014817.4(TRIL):āc.2084A>Gā(p.Tyr695Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000193 in 1,553,190 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ).
Frequency
Genomes: š 0.0000066 ( 0 hom., cov: 34)
Exomes š: 0.0000014 ( 0 hom. )
Consequence
TRIL
NM_014817.4 missense
NM_014817.4 missense
Scores
3
2
6
Clinical Significance
Conservation
PhyloP100: 1.91
Genes affected
TRIL (HGNC:22200): (TLR4 interactor with leucine rich repeats) TRIL is a component of the TLR4 (MIM 603030) complex and is induced in a number of cell types by lipopolysaccharide (LPS) (Carpenter et al., 2009 [PubMed 19710467]).[supplied by OMIM, Apr 2010]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 1 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.35906047).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
TRIL | NM_014817.4 | c.2084A>G | p.Tyr695Cys | missense_variant | 1/1 | ENST00000539664.3 | NP_055632.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
TRIL | ENST00000539664.3 | c.2084A>G | p.Tyr695Cys | missense_variant | 1/1 | NM_014817.4 | ENSP00000479256 | P1 |
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152188Hom.: 0 Cov.: 34
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GnomAD3 exomes AF: 0.00000649 AC: 1AN: 153994Hom.: 0 AF XY: 0.0000119 AC XY: 1AN XY: 84092
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GnomAD4 exome AF: 0.00000143 AC: 2AN: 1401002Hom.: 0 Cov.: 30 AF XY: 0.00000144 AC XY: 1AN XY: 692292
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GnomAD4 genome AF: 0.00000657 AC: 1AN: 152188Hom.: 0 Cov.: 34 AF XY: 0.00 AC XY: 0AN XY: 74340
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Dec 14, 2023 | The c.2084A>G (p.Y695C) alteration is located in exon 1 (coding exon 1) of the TRIL gene. This alteration results from a A to G substitution at nucleotide position 2084, causing the tyrosine (Y) at amino acid position 695 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Pathogenic
DANN
Benign
DEOGEN2
Benign
T
FATHMM_MKL
Pathogenic
D
LIST_S2
Benign
T
MetaRNN
Benign
T
MutationAssessor
Benign
N
PrimateAI
Uncertain
T
Sift4G
Benign
T
Polyphen
D
Vest4
MVP
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at