11-66473383-C-G

Position:

• chr11-66473383-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_145065.3(PELI3):​c.599C>G​(p.Thr200Ser) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: PELI3 NM_145065.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.10

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 (HGNC:):

ACMG classification

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=0.3888796).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PELI3	NM_145065.3	c.599C>G	p.Thr200Ser	missense_variant	6/8	ENST00000320740.12	NP_659502.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PELI3	ENST00000320740.12	c.599C>G	p.Thr200Ser	missense_variant	6/8	1	NM_145065.3	ENSP00000322532.7

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 28, 2024

The c.599C>G (p.T200S) alteration is located in exon 6 (coding exon 5) of the PELI3 gene. This alteration results from a C to G substitution at nucleotide position 599, causing the threonine (T) at amino acid position 200 to be replaced by a serine (S). 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	0.11
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.46
CADD	Benign	21
DANN	Uncertain	0.97
DEOGEN2	Benign	0.036	.;.;T;.;.
Eigen	Uncertain	0.24
Eigen_PC	Uncertain	0.28
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Uncertain	0.89	D;D;D;D;D
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.39	T;T;T;T;T
MetaSVM	Benign	-0.89	T
MutationAssessor	Benign	1.4	.;.;L;L;.
PrimateAI	Uncertain	0.63	T
PROVEAN	Benign	-1.9	.;N;N;N;N
REVEL	Benign	0.13
Sift	Benign	0.15	.;T;T;T;T
Sift4G	Benign	0.35	T;T;T;T;T
Polyphen		0.017, 0.73, 0.81	.;B;P;P;.
Vest4		0.17
MutPred		0.63		.;.;Gain of sheet (P = 0.0344);Gain of sheet (P = 0.0344);.;
MVP		0.68
MPC		1.7
ClinPred		0.82	D
GERP RS		4.3
Varity_R		0.21
gMVP		0.33

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.

Other links and lift over

hg19: chr11-66240854;