11-66475806-C-T

Variant names:

• chr11-66475806-C-T
• rs751096914
• NM_145065.3:c.1049C>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.1049C>T​(p.Ala350Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000498 in 1,607,748 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0000048 (0 hom.)
• Consequence: PELI3 NM_145065.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.16
• Publications: 4 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=0.0720267).

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.1049C>T	p.Ala350Val	missense	Exon 8 of 8	NP_659502.2	Q8N2H9-1
	PELI3	NM_001098510.2		c.977C>T	p.Ala326Val	missense	Exon 7 of 7	NP_001091980.1	Q8N2H9-2
	PELI3	NM_001243135.2		c.860C>T	p.Ala287Val	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.1049C>T	p.Ala350Val	missense	Exon 8 of 8	ENSP00000322532.7	Q8N2H9-1
	PELI3	ENST00000349459.10	TSL:1	c.977C>T	p.Ala326Val	missense	Exon 7 of 7	ENSP00000309848.8	Q8N2H9-2
	PELI3	ENST00000904606.1		c.1049C>T	p.Ala350Val	missense	Exon 8 of 8	ENSP00000574665.1

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152244 Hom.: 0 Cov.: 33

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

GnomAD2 exomes AF: 0.00000883 AC: 2 AN: 226384 AF XY: 0.0000160

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.000178

GnomAD4 exome AF: 0.00000481 AC: 7 AN: 1455504 Hom.: 0 Cov.: 31 AF XY: 0.00000553 AC XY: 4 AN XY: 723930

African (AFR) AF: 0.00 AC: 0 AN: 33366

American (AMR) AF: 0.00 AC: 0 AN: 44144

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 39486

South Asian (SAS) AF: 0.0000117 AC: 1 AN: 85748

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51004

Middle Eastern (MID) AF: 0.000360 AC: 2 AN: 5558

European-Non Finnish (NFE) AF: 0.00000360 AC: 4 AN: 1110136

Other (OTH) AF: 0.00 AC: 0 AN: 60052

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152244 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 74380

African (AFR) AF: 0.00 AC: 0 AN: 41460

American (AMR) AF: 0.00 AC: 0 AN: 15294

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5202

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: 0.0000147 AC: 1 AN: 68030

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

Alfa AF: 0.0000434 Hom.: 0

Bravo AF: 0.00000378

ExAC AF: 0.0000251 AC: 3

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	0.070
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.62
CADD	Benign	21
DANN	Benign	0.78
DEOGEN2	Benign	0.0089	T
Eigen	Benign	-0.68
Eigen_PC	Benign	-0.46
FATHMM_MKL	Benign	0.38	N
LIST_S2	Benign	0.81	T
M_CAP	Benign	0.0072	T
MetaRNN	Benign	0.072	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	0.14	N
PhyloP100		3.2
PrimateAI	Uncertain	0.61	T
PROVEAN	Benign	0.44	N
REVEL	Benign	0.070
Sift	Benign	0.77	T
Sift4G	Benign	0.64	T
Polyphen		0.0010	B
Vest4		0.043
MutPred		0.25		Gain of MoRF binding (P = 0.112)
MVP		0.46
MPC		0.74
ClinPred		0.096	T
GERP RS		4.2
Varity_R		0.040
gMVP		0.37
Mutation Taster		=94/6	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: rs751096914; hg19: chr11-66243277; COSMIC: COSV57857601; COSMIC: COSV57857601;