rs199980830

Variant names:

• chr11-66468160-C-A
• NM_145065.3:c.32C>A

Your query was ambiguous. Multiple possible variants found:

• chr11-66468160-C-A
• chr11-66468160-C-G
• chr11-66468160-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 4P and 2B. PM1 PM2 BP4_Moderate

The NM_145065.3(PELI3):​c.32C>A​(p.Ser11Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000688 in 1,454,494 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 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. S11F) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: PELI3 NM_145065.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.67

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM1: In a modified_residue Phosphoserine (size 0) in uniprot entity PELI3_HUMAN
• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.1901575).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PELI3	NM_145065.3	c.32C>A	p.Ser11Tyr	missense_variant	Exon 2 of 8	ENST00000320740.12	NP_659502.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PELI3	ENST00000320740.12	c.32C>A	p.Ser11Tyr	missense_variant	Exon 2 of 8	1	NM_145065.3	ENSP00000322532.7

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.88e-7 AC: 1 AN: 1454494 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 723342

Gnomad4 AFR exome AF: 0.0000303

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.39
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.017	.;.;T;.;T
Eigen	Benign	0.032
Eigen_PC	Benign	0.16
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.86	D;D;D;D;D
M_CAP	Benign	0.021	T
MetaRNN	Benign	0.19	T;T;T;T;T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	0.90	L;L;L;L;.
PrimateAI	Benign	0.43	T
PROVEAN	Benign	-0.47	.;N;N;N;N
REVEL	Benign	0.059
Sift	Uncertain	0.010	.;D;D;D;D
Sift4G	Uncertain	0.056	T;T;T;T;D
Polyphen		0.32, 0.42, 0.55	.;B;B;P;.
Vest4		0.57
MutPred		0.20		Gain of catalytic residue at S11 (P = 0.0545);Gain of catalytic residue at S11 (P = 0.0545);Gain of catalytic residue at S11 (P = 0.0545);Gain of catalytic residue at S11 (P = 0.0545);Gain of catalytic residue at S11 (P = 0.0545);
MVP		0.68
MPC		1.0
ClinPred		0.72	D
GERP RS		5.1
Varity_R		0.12
gMVP		0.14

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: chr11-66235631;