2-64095064-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_020651.4(PELI1):c.895G>T(p.Val299Phe) 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: PELI1 NM_020651.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.94

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

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.33300483).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PELI1	NM_020651.4	c.895G>T	p.Val299Phe	missense_variant	7/7	ENST00000358912.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PELI1	ENST00000358912.5	c.895G>T	p.Val299Phe	missense_variant	7/7	1	NM_020651.4	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 17, 2023

The c.895G>T (p.V299F) alteration is located in exon 7 (coding exon 6) of the PELI1 gene. This alteration results from a G to T substitution at nucleotide position 895, causing the valine (V) at amino acid position 299 to be replaced by a phenylalanine (F). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Benign	-0.071	T
BayesDel_noAF	Benign	-0.34
Cadd	Pathogenic	27
Dann	Benign	0.97
DEOGEN2	Benign	0.11	T
Eigen	Uncertain	0.47
Eigen_PC	Uncertain	0.55
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Uncertain	0.96	D
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.33	T
MetaSVM	Benign	-0.92	T
MutationAssessor	Uncertain	2.1	M
MutationTaster	Benign	1.0	D
PrimateAI	Uncertain	0.78	T
PROVEAN	Benign	-1.4	N
REVEL	Benign	0.077
Sift	Benign	0.22	T
Sift4G	Benign	0.22	T
Polyphen		0.75	P
Vest4		0.51
MutPred		0.29		Loss of sheet (P = 0.1158);
MVP		0.31
MPC		1.3
ClinPred		0.52	D
GERP RS		5.8
Varity_R		0.22
gMVP		0.47

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr2-64322198;