Variant chr11-66468219-C-G details in Genebe, Genetics Data Aggregator

Variant summary

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

The ENST00000320740.12(PELI3):c.91C>G(p.Pro31Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000069 in 1,449,500 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

PELI3
ENST00000320740.12 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.22

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]

PELI3 links:

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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=0.17380553).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PELI3	NM_145065.3 linkuse as main transcript	c.91C>G	p.Pro31Ala	missense_variant	2/8	ENST00000320740.12	NP_659502.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PELI3	ENST00000320740.12 linkuse as main transcript	c.91C>G	p.Pro31Ala	missense_variant	2/8	1	NM_145065.3	ENSP00000322532		Q8N2H9-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.90e-7

AC:

AN:

1449500

Hom.:

Cov.:

AF XY:

0.00000139

AC XY:

AN XY:

720110

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:

9.05e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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

Feb 16, 2023

The c.91C>G (p.P31A) alteration is located in exon 2 (coding exon 1) of the PELI3 gene. This alteration results from a C to G substitution at nucleotide position 91, causing the proline (P) at amino acid position 31 to be replaced by an alanine (A). 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

0.053

BayesDel_addAF

Benign

-0.18

BayesDel_noAF

Benign

-0.50

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.013

.;.;T;.;T

Eigen

Benign

-0.16

Eigen_PC

Benign

-0.042

FATHMM_MKL

Uncertain

0.86

LIST_S2

Benign

0.85

T;T;T;T;T

M_CAP

Benign

0.016

MetaRNN

Benign

0.17

T;T;T;T;T

MetaSVM

Benign

-0.94

MutationAssessor

Benign

0.49

N;N;N;N;.

MutationTaster

Benign

0.92

D;D;D

PrimateAI

Benign

0.35

PROVEAN

Benign

-0.55

.;N;N;N;N

REVEL

Benign

0.045

Sift

Benign

0.030

.;D;D;T;T

Sift4G

Benign

0.24

T;T;T;T;T

Polyphen

0.021, 0.0010, 0.041

.;B;B;B;.

Vest4

0.22

MutPred

0.44

Loss of stability (P = 0.0113);Loss of stability (P = 0.0113);Loss of stability (P = 0.0113);Loss of stability (P = 0.0113);Loss of stability (P = 0.0113);

MVP

0.54

MPC

0.72

ClinPred

0.21

GERP RS

4.2

Varity_R

0.073

gMVP

0.13

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over