11-66476157-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_145065.3(PELI3):​c.1400C>T​(p.Pro467Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000103 in 1,551,414 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000011 ( 0 hom. )

Consequence

PELI3
NM_145065.3 missense

Scores

7
7
5

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.91
Variant links:
Genes affected
PELI3 (HGNC:30010): (pellino E3 ubiquitin protein ligase family member 3) The protein encoded by this gene is a scaffold protein and an intermediate signaling protein in the innate immune response pathway. The encoded protein helps transmit the immune response signal from Toll-like receptors to IRAK1/TRAF6 complexes. Several transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Jul 2011]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.812

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
PELI3NM_145065.3 linkuse as main transcriptc.1400C>T p.Pro467Leu missense_variant 8/8 ENST00000320740.12 NP_659502.2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
PELI3ENST00000320740.12 linkuse as main transcriptc.1400C>T p.Pro467Leu missense_variant 8/81 NM_145065.3 ENSP00000322532.7 Q8N2H9-1

Frequencies

GnomAD3 genomes
AF:
0.00000657
AC:
1
AN:
152220
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000147
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000253
AC:
4
AN:
158112
Hom.:
0
AF XY:
0.0000230
AC XY:
2
AN XY:
86814
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.000151
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000107
AC:
15
AN:
1399194
Hom.:
0
Cov.:
31
AF XY:
0.0000130
AC XY:
9
AN XY:
692458
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000789
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.0000277
Gnomad4 NFE exome
AF:
0.00000920
Gnomad4 OTH exome
AF:
0.0000172
GnomAD4 genome
AF:
0.00000657
AC:
1
AN:
152220
Hom.:
0
Cov.:
33
AF XY:
0.00
AC XY:
0
AN XY:
74358
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000147
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000113

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 16, 2022The c.1400C>T (p.P467L) alteration is located in exon 8 (coding exon 7) of the PELI3 gene. This alteration results from a C to T substitution at nucleotide position 1400, causing the proline (P) at amino acid position 467 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
Uncertain
0.45
BayesDel_addAF
Benign
-0.0017
T
BayesDel_noAF
Uncertain
0.020
CADD
Pathogenic
33
DANN
Pathogenic
1.0
DEOGEN2
Benign
0.11
.;.;T
Eigen
Pathogenic
0.80
Eigen_PC
Pathogenic
0.74
FATHMM_MKL
Uncertain
0.94
D
LIST_S2
Pathogenic
1.0
D;D;D
M_CAP
Benign
0.036
D
MetaRNN
Pathogenic
0.81
D;D;D
MetaSVM
Benign
-0.40
T
MutationAssessor
Uncertain
2.1
.;.;M
PrimateAI
Pathogenic
0.82
D
PROVEAN
Pathogenic
-4.5
.;D;D
REVEL
Uncertain
0.43
Sift
Uncertain
0.0070
.;D;D
Sift4G
Uncertain
0.028
D;D;D
Polyphen
1.0
.;D;D
Vest4
0.70
MutPred
0.59
.;.;Gain of sheet (P = 0.0477);
MVP
0.85
MPC
1.8
ClinPred
0.93
D
GERP RS
4.6
Varity_R
0.31
gMVP
0.51

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs892880404; hg19: chr11-66243628; API