11-66473290-C-T

Variant names:

• chr11-66473290-C-T
• rs149736299
• NM_145065.3:c.506C>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_145065.3(PELI3):​c.506C>T​(p.Ser169Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000186 in 1,613,402 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S169C) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: PELI3 NM_145065.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.712
• Publications: 3 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.13407299).

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.506C>T	p.Ser169Phe	missense	Exon 6 of 8	NP_659502.2	Q8N2H9-1
	PELI3	NM_001098510.2		c.434C>T	p.Ser145Phe	missense	Exon 5 of 7	NP_001091980.1	Q8N2H9-2
	PELI3	NM_001243135.2		c.317C>T	p.Ser106Phe	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.506C>T	p.Ser169Phe	missense	Exon 6 of 8	ENSP00000322532.7	Q8N2H9-1
	PELI3	ENST00000349459.10	TSL:1	c.434C>T	p.Ser145Phe	missense	Exon 5 of 7	ENSP00000309848.8	Q8N2H9-2
	PELI3	ENST00000524466.5	TSL:1	c.506C>T	p.Ser169Phe	missense	Exon 6 of 7	ENSP00000434677.1	Q8N2H9-4

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152180 Hom.: 0 Cov.: 32

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

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461222 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 726934

African (AFR) AF: 0.00 AC: 0 AN: 33474

American (AMR) AF: 0.00 AC: 0 AN: 44708

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26118

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.00 AC: 0 AN: 86242

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52930

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00000180 AC: 2 AN: 1111902

Other (OTH) AF: 0.00 AC: 0 AN: 60382

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152180 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74334

African (AFR) AF: 0.00 AC: 0 AN: 41440

American (AMR) AF: 0.00 AC: 0 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5206

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10616

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68016

Other (OTH) AF: 0.00 AC: 0 AN: 2090

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.45
CADD	Benign	23
DANN	Benign	0.68
DEOGEN2	Benign	0.014	T
Eigen	Benign	-0.25
Eigen_PC	Benign	-0.16
FATHMM_MKL	Benign	0.23	N
LIST_S2	Uncertain	0.97	D
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.13	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.90	L
PhyloP100		0.71
PrimateAI	Uncertain	0.63	T
PROVEAN	Benign	0.070	N
REVEL	Benign	0.083
Sift	Benign	0.55	T
Sift4G	Benign	0.41	T
Polyphen		0.14	B
Vest4		0.37
MutPred		0.31		Loss of disorder (P = 0.0121)
MVP		0.55
MPC		1.2
ClinPred		0.48	T
GERP RS		4.2
PromoterAI		-0.0063	Neutral
Varity_R		0.069
gMVP		0.22
Mutation Taster		=93/7	polymorphism

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

Other links and lift over

dbSNP: rs149736299; hg19: chr11-66240761;