Genetic Variant PAN3:p.Pro77Ser (chr13-28138886-C-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_175854.8(PAN3):c.229C>T(p.Pro77Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 30)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

PAN3
NM_175854.8 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.23

Variant links:

Genes affected

PAN3 (HGNC:29991): (poly(A) specific ribonuclease subunit PAN3) Contributes to poly(A)-specific ribonuclease activity. Predicted to be involved in nuclear-transcribed mRNA poly(A) tail shortening. Predicted to act upstream of or within deadenylation-dependent decapping of nuclear-transcribed mRNA; positive regulation of cytoplasmic mRNA processing body assembly; and protein targeting. Part of PAN complex. [provided by Alliance of Genome Resources, Apr 2022]

PAN3 links:

PAN3-AS1 (HGNC:39932): (PAN3 antisense RNA 1)

PAN3-AS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.11238864).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PAN3	NM_175854.8 link	c.229C>T	p.Pro77Ser	missense_variant	Exon 1 of 19	ENST00000380958.8	NP_787050.6	Q58A45-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
PAN3	ENST00000380958.8 link	c.229C>T	p.Pro77Ser	missense_variant	Exon 1 of 19	5	NM_175854.8	ENSP00000370345.3	Q58A45-1
PAN3	ENST00000503791.5 link	n.381C>T		non_coding_transcript_exon_variant	Exon 1 of 14	2
PAN3	ENST00000399613.1 link	c.-210C>T		upstream_gene_variant		5		ENSP00000382522.1	A0A0C4DFZ9

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1259480

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

617710

Gnomad4 AFR exome

AF:

0.00

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.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Jul 07, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.229C>T (p.P77S) alteration is located in exon 1 (coding exon 1) of the PAN3 gene. This alteration results from a C to T substitution at nucleotide position 229, causing the proline (P) at amino acid position 77 to be replaced by a serine (S). 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

0.073

BayesDel_addAF

Benign

-0.18

BayesDel_noAF

Benign

-0.49

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.012

Eigen

Benign

-0.53

Eigen_PC

Benign

-0.40

FATHMM_MKL

Benign

0.33

LIST_S2

Benign

0.82

M_CAP

Pathogenic

0.35

MetaRNN

Benign

0.11

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.0

PrimateAI

Pathogenic

0.87

PROVEAN

Benign

-0.51

REVEL

Benign

0.028

Sift

Uncertain

0.0080

Sift4G

Uncertain

0.027

Vest4

0.072

MutPred

0.32

Gain of glycosylation at P77 (P = 0.0099);

MVP

0.082

MPC

0.46

ClinPred

0.58

GERP RS

2.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.8

Varity_R

0.16

gMVP

0.15

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over