chr7-28955993-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_014817.4(TRIL):​c.2054C>T​(p.Pro685Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000286 in 1,399,888 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 (★).

Frequency

Genomes: not found (cov: 34)
Exomes 𝑓: 0.0000029 ( 0 hom. )

Consequence

TRIL
NM_014817.4 missense

Scores

2
2
7

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.18
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

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=0.23895591).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
TRILNM_014817.4 linkuse as main transcriptc.2054C>T p.Pro685Leu missense_variant 1/1 ENST00000539664.3 NP_055632.2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
TRILENST00000539664.3 linkuse as main transcriptc.2054C>T p.Pro685Leu missense_variant 1/1 NM_014817.4 ENSP00000479256 P1

Frequencies

GnomAD3 genomes
Cov.:
34
GnomAD4 exome
AF:
0.00000286
AC:
4
AN:
1399888
Hom.:
0
Cov.:
30
AF XY:
0.00000145
AC XY:
1
AN XY:
691886
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000368
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
34

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 submitterclinical testingAmbry GeneticsAug 11, 2022The c.2054C>T (p.P685L) alteration is located in exon 1 (coding exon 1) of the TRIL gene. This alteration results from a C to T substitution at nucleotide position 2054, causing the proline (P) at amino acid position 685 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.34
BayesDel_addAF
Uncertain
0.059
T
BayesDel_noAF
Benign
-0.15
CADD
Pathogenic
29
DANN
Benign
0.97
DEOGEN2
Benign
0.068
T
FATHMM_MKL
Pathogenic
1.0
D
LIST_S2
Benign
0.85
T
MetaRNN
Benign
0.24
T
MutationAssessor
Benign
0.90
L
PrimateAI
Uncertain
0.74
T
Sift4G
Pathogenic
0.0
D
Polyphen
0.95
P
Vest4
0.33
MVP
0.27
GERP RS
5.0
Varity_R
0.25
gMVP
0.39

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: chr7-28995609; API