chr11-66475799-C-T

Variant names:

• chr11-66475799-C-T
• rs201923086
• NM_145065.3:c.1042C>T

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BP4

The NM_145065.3(PELI3):​c.1042C>T​(p.Arg348Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000121 in 1,608,274 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R348H) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.00011 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00012 (0 hom.)
• Consequence: PELI3 NM_145065.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.44
• Publications: 1 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: Likely_benign. The variant received -1 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.29639268).

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.1042C>T	p.Arg348Cys	missense	Exon 8 of 8	NP_659502.2	Q8N2H9-1
	PELI3	NM_001098510.2		c.970C>T	p.Arg324Cys	missense	Exon 7 of 7	NP_001091980.1	Q8N2H9-2
	PELI3	NM_001243135.2		c.853C>T	p.Arg285Cys	missense	Exon 7 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.1042C>T	p.Arg348Cys	missense	Exon 8 of 8	ENSP00000322532.7	Q8N2H9-1
	PELI3	ENST00000349459.10	TSL:1	c.970C>T	p.Arg324Cys	missense	Exon 7 of 7	ENSP00000309848.8	Q8N2H9-2
	PELI3	ENST00000904606.1		c.1042C>T	p.Arg348Cys	missense	Exon 8 of 8	ENSP00000574665.1

Frequencies

GnomAD3 genomes AF: 0.000105 AC: 16 AN: 152224 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000482

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000654

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: 0.000191

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000571 AC: 13 AN: 227590 AF XY: 0.0000558

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000299

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000112

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000122 AC: 178 AN: 1456050 Hom.: 0 Cov.: 31 AF XY: 0.0000980 AC XY: 71 AN XY: 724166

African (AFR) AF: 0.0000899 AC: 3 AN: 33366

American (AMR) AF: 0.0000904 AC: 4 AN: 44232

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26010

East Asian (EAS) AF: 0.0000253 AC: 1 AN: 39504

South Asian (SAS) AF: 0.0000117 AC: 1 AN: 85816

European-Finnish (FIN) AF: 0.0000195 AC: 1 AN: 51154

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5556

European-Non Finnish (NFE) AF: 0.000140 AC: 156 AN: 1110326

Other (OTH) AF: 0.000200 AC: 12 AN: 60086

GnomAD4 genome AF: 0.000105 AC: 16 AN: 152224 Hom.: 0 Cov.: 33 AF XY: 0.0000538 AC XY: 4 AN XY: 74370

African (AFR) AF: 0.0000482 AC: 2 AN: 41460

American (AMR) AF: 0.0000654 AC: 1 AN: 15290

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5196

South Asian (SAS) AF: 0.00 AC: 0 AN: 4836

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10628

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

European-Non Finnish (NFE) AF: 0.000191 AC: 13 AN: 68022

Other (OTH) AF: 0.00 AC: 0 AN: 2094

Alfa AF: 0.000408 Hom.: 0

Bravo AF: 0.000117

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000119 AC: 1

ExAC AF: 0.0000669 AC: 8

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	0.15
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.37
CADD	Pathogenic	34
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.039	T
Eigen	Uncertain	0.46
Eigen_PC	Uncertain	0.46
FATHMM_MKL	Uncertain	0.87	D
LIST_S2	Uncertain	0.93	D
M_CAP	Benign	0.035	D
MetaRNN	Benign	0.30	T
MetaSVM	Benign	-0.89	T
MutationAssessor	Benign	1.5	L
PhyloP100		2.4
PrimateAI	Uncertain	0.72	T
PROVEAN	Benign	-1.8	N
REVEL	Benign	0.12
Sift	Uncertain	0.028	D
Sift4G	Uncertain	0.047	D
Polyphen		1.0	D
Vest4		0.24
MVP		0.81
MPC		2.1
ClinPred		0.37	T
GERP RS		5.2
Varity_R		0.17
gMVP		0.66
Mutation Taster		=76/24	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: rs201923086; hg19: chr11-66243270; COSMIC: COSV57856296; COSMIC: COSV57856296;