11-66473383-C-G

Variant names:

• chr11-66473383-C-G
• NM_145065.3:c.599C>G

Variant summary

Our verdict is Uncertain significance. The variant received 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. Variant has been reported in ClinVar as Uncertain significance (★).

• 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
• Publications: 0 publications found

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]

DPP3-DT (HGNC:55494): (DPP3 divergent transcript)

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3888796).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_145065.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PELI3	NM_145065.3	MANE Select	c.599C>G	p.Thr200Ser	missense	Exon 6 of 8	NP_659502.2	Q8N2H9-1
	PELI3	NM_001098510.2		c.527C>G	p.Thr176Ser	missense	Exon 5 of 7	NP_001091980.1	Q8N2H9-2
	PELI3	NM_001243135.2		c.410C>G	p.Thr137Ser	missense	Exon 5 of 7	NP_001230064.1	Q8N2H9-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PELI3	ENST00000320740.12	TSL:1 MANE Select	c.599C>G	p.Thr200Ser	missense	Exon 6 of 8	ENSP00000322532.7	Q8N2H9-1
	PELI3	ENST00000349459.10	TSL:1	c.527C>G	p.Thr176Ser	missense	Exon 5 of 7	ENSP00000309848.8	Q8N2H9-2
	PELI3	ENST00000524466.5	TSL:1	c.599C>G	p.Thr200Ser	missense	Exon 6 of 7	ENSP00000434677.1	Q8N2H9-4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

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
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.39	T
MetaSVM	Benign	-0.89	T
MutationAssessor	Benign	1.4	L
PhyloP100		4.1
PrimateAI	Uncertain	0.63	T
PROVEAN	Benign	-1.9	N
REVEL	Benign	0.13
Sift	Benign	0.15	T
Sift4G	Benign	0.35	T
Polyphen		0.017	B
Vest4		0.17
MutPred		0.63		Gain of sheet (P = 0.0344)
MVP		0.68
MPC		1.7
ClinPred		0.82	D
GERP RS		4.3
PromoterAI		-0.023	Neutral
Varity_R		0.21
gMVP		0.33
Mutation Taster		=80/20	polymorphism

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

Other links and lift over

hg19: chr11-66240854;