NM_020651.4:c.1166A>G

Variant names:

• chr2-64094793-T-C
• rs772404166
• NM_020651.4:c.1166A>G

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_020651.4(PELI1):​c.1166A>G​(p.His389Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: PELI1 NM_020651.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 8.02
• Publications: 1 publications found

Genes affected

PELI1 (HGNC:8827): (pellino E3 ubiquitin protein ligase 1) Enables ubiquitin protein ligase activity. Involved in several processes, including negative regulation of necroptotic process; protein polyubiquitination; and response to lipopolysaccharide. Predicted to be located in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.799

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020651.4. 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
	PELI1	NM_020651.4	MANE Select	c.1166A>G	p.His389Arg	missense	Exon 7 of 7	NP_065702.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PELI1	ENST00000358912.5	TSL:1 MANE Select	c.1166A>G	p.His389Arg	missense	Exon 7 of 7	ENSP00000351789.4	Q96FA3
	PELI1	ENST00000903228.1		c.1235A>G	p.His412Arg	missense	Exon 8 of 8	ENSP00000573287.1
	PELI1	ENST00000924986.1		c.1187A>G	p.His396Arg	missense	Exon 7 of 7	ENSP00000595045.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

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	Pathogenic	0.99
BayesDel_addAF	Uncertain	0.085	D
BayesDel_noAF	Benign	-0.12
CADD	Pathogenic	28
DANN	Uncertain	1.0
DEOGEN2	Benign	0.37	T
Eigen	Pathogenic	0.82
Eigen_PC	Pathogenic	0.81
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Pathogenic	0.98	D
M_CAP	Benign	0.024	T
MetaRNN	Pathogenic	0.80	D
MetaSVM	Benign	-0.59	T
MutationAssessor	Uncertain	2.8	M
PhyloP100		8.0
PrimateAI	Pathogenic	0.87	D
PROVEAN	Uncertain	-3.6	D
REVEL	Uncertain	0.38
Sift	Uncertain	0.028	D
Sift4G	Benign	0.14	T
Polyphen		1.0	D
Vest4		0.61
MutPred		0.71		Loss of glycosylation at T388 (P = 0.0828)
MVP		0.62
MPC		1.3
ClinPred		0.98	D
GERP RS		5.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.59
gMVP		0.50
Mutation Taster		=57/43	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: rs772404166; hg19: chr2-64321927;