Genetic Variant NM_175854.8:c.23C>T (chr13-28138680-C-T) – 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>T(p.Pro8Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000004 in 750,798 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 29)

Exomes 𝑓: 0.0000040 ( 0 hom. )

Consequence

PAN3
NM_175854.8 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

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=0.18661314).

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>T	p.Pro8Leu	missense	Exon 1 of 19	NP_787050.6
	PAN3-AS1	NR_029383.1		n.495G>A		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>T	p.Pro8Leu	missense	Exon 1 of 19	ENSP00000370345.3	Q58A45-1
PAN3	ENST00000913194.1		c.23C>T	p.Pro8Leu	missense	Exon 1 of 18	ENSP00000583253.1
PAN3	ENST00000503791.5	TSL:2	n.175C>T		non_coding_transcript_exon	Exon 1 of 14

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000400

AC:

AN:

750798

Hom.:

Cov.:

AF XY:

0.00000267

AC XY:

AN XY:

374554

show subpopulations

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:

0.0000608

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:

0.00000168

AC:

AN:

593706

Other (OTH)

AF:

0.00

AC:

AN:

33376

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.608

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.15

BayesDel_addAF

Benign

-0.062

BayesDel_noAF

Benign

-0.33

CADD

Uncertain

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.013

Eigen

Benign

-0.45

Eigen_PC

Benign

-0.32

FATHMM_MKL

Benign

0.35

LIST_S2

Benign

0.85

M_CAP

Pathogenic

0.80

MetaRNN

Benign

0.19

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.55

PhyloP100

0.60

PrimateAI

Pathogenic

0.88

PROVEAN

Benign

-0.060

REVEL

Benign

0.12

Sift

Pathogenic

0.0

Sift4G

Uncertain

0.010

Vest4

0.20

MutPred

0.10

Loss of glycosylation at P8 (P = 0.0301)

MVP

0.36

MPC

1.8

ClinPred

0.50

GERP RS

2.6

PromoterAI

-0.037

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.15

gMVP

0.28

Mutation Taster

=92/8

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over