Genetic Variant PAN3:p.Ser192Phe (chr13-28176515-C-T) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_175854.8(PAN3):c.575C>T(p.Ser192Phe) variant causes a missense change. The variant allele was found at a frequency of 0.00000274 in 1,461,626 control chromosomes in the GnomAD database, with no homozygous occurrence. 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)

Exomes 𝑓: 0.0000027 ( 0 hom. )

Consequence

PAN3
NM_175854.8 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.72

Publications

1 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:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.39951974).

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.575C>T	p.Ser192Phe	missense	Exon 3 of 19	NP_787050.6

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PAN3	ENST00000380958.8	TSL:5 MANE Select	c.575C>T	p.Ser192Phe	missense	Exon 3 of 19	ENSP00000370345.3	Q58A45-1
PAN3	ENST00000913194.1		c.575C>T	p.Ser192Phe	missense	Exon 3 of 18	ENSP00000583253.1
PAN3	ENST00000399613.1	TSL:5	c.137C>T	p.Ser46Phe	missense	Exon 3 of 18	ENSP00000382522.1	A0A0C4DFZ9

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000398

AC:

AN:

251226

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000544

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000274

AC:

AN:

1461626

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727130

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33468

American (AMR)

AF:

0.00

AC:

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26124

East Asian (EAS)

AF:

0.0000756

AC:

AN:

39670

South Asian (SAS)

AF:

0.00

AC:

AN:

86252

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53408

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

8.99e-7

AC:

AN:

1111834

Other (OTH)

AF:

0.00

AC:

AN:

60382

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.463

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.:

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

Pathogenic

0.83

BayesDel_addAF

Uncertain

0.16

BayesDel_noAF

Uncertain

-0.010

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.032

Eigen

Uncertain

0.68

Eigen_PC

Pathogenic

0.71

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Pathogenic

0.98

M_CAP

Benign

0.081

MetaRNN

Benign

0.40

MetaSVM

Benign

-0.35

MutationAssessor

Benign

0.69

PhyloP100

6.7

PrimateAI

Uncertain

0.70

PROVEAN

Benign

-1.6

REVEL

Benign

0.26

Sift

Pathogenic

0.0

Sift4G

Uncertain

0.026

Polyphen

0.99

Vest4

0.59

MutPred

0.15

Loss of phosphorylation at S192 (P = 0.0268)

MVP

0.42

MPC

0.61

ClinPred

0.80

GERP RS

5.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.53

gMVP

0.70

Mutation Taster

=52/48

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