Genetic Variant NM_175854.8:c.23C>A (chr13-28138680-C-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_175854.8(PAN3):c.23C>A(p.Pro8Gln) 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. 14/22 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. P8L) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 29)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

PAN3
NM_175854.8 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.597

Publications

0 publications found

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:

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ACMG classification

Classification was made for transcript

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=0.24146268).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_175854.8. 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
	PAN3	NM_175854.8	MANE Select	c.23C>A	p.Pro8Gln	missense	Exon 1 of 19	NP_787050.6
	PAN3-AS1	NR_029383.1		n.495G>T		non_coding_transcript_exon	Exon 1 of 2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PAN3	ENST00000380958.8	TSL:5 MANE Select	c.23C>A	p.Pro8Gln	missense	Exon 1 of 19	ENSP00000370345.3	Q58A45-1
PAN3	ENST00000913194.1		c.23C>A	p.Pro8Gln	missense	Exon 1 of 18	ENSP00000583253.1
PAN3	ENST00000503791.5	TSL:2	n.175C>A		non_coding_transcript_exon	Exon 1 of 14

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

750802

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

374558

African (AFR)

AF:

0.00

AC:

AN:

15028

American (AMR)

AF:

0.00

AC:

AN:

8164

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

13094

East Asian (EAS)

AF:

0.00

AC:

AN:

25064

South Asian (SAS)

AF:

0.00

AC:

AN:

32882

European-Finnish (FIN)

AF:

0.00

AC:

AN:

25868

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3616

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

593710

Other (OTH)

AF:

0.00

AC:

AN:

33376

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.037

BayesDel_noAF

Benign

-0.29

CADD

Uncertain

(source)

DANN

Benign

0.97

DEOGEN2

Benign

0.013

Eigen

Benign

-0.026

Eigen_PC

Benign

-0.020

FATHMM_MKL

Benign

0.67

LIST_S2

Benign

0.76

M_CAP

Pathogenic

0.76

MetaRNN

Benign

0.24

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.55

PhyloP100

0.60

PrimateAI

Pathogenic

0.86

PROVEAN

Benign

-0.21

REVEL

Benign

0.18

Sift

Pathogenic

0.0

Sift4G

Uncertain

0.011

Vest4

0.22

MutPred

0.077

Loss of glycosylation at P8 (P = 0.0301)

MVP

0.44

MPC

1.7

ClinPred

0.54

GERP RS

2.6

PromoterAI

-0.12

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.17

gMVP

0.32

Mutation Taster

=89/11

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over