Variant 9-2828765-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_014878.5(PUM3):c.866G>C(p.Arg289Pro) variant causes a missense change. The variant allele was found at a frequency of 0.553 in 1,576,500 control chromosomes in the GnomAD database, including 243,751 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/19 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 nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.57 ( 25298 hom., cov: 33)

Exomes 𝑓: 0.55 ( 218453 hom. )

Consequence

PUM3
NM_014878.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.81

Variant links:

Genes affected

PUM3 (HGNC:29676): (pumilio RNA binding family member 3) Enables RNA binding activity. Involved in regulation of protein ADP-ribosylation. Located in chromosome; endoplasmic reticulum; and nuclear lumen. [provided by Alliance of Genome Resources, Apr 2022]

PUM3 links:

PUM3 (HGNC:):

PUM3 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=5.775965E-5).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.619 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PUM3	NM_014878.5 linkuse as main transcript	c.866G>C	p.Arg289Pro	missense_variant	9/18	ENST00000397885.3	NP_055693.4	Q15397

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PUM3	ENST00000397885.3 linkuse as main transcript	c.866G>C	p.Arg289Pro	missense_variant	9/18	1	NM_014878.5	ENSP00000380982.2		Q15397
PUM3	ENST00000469168.1 linkuse as main transcript	n.166G>C		non_coding_transcript_exon_variant	2/2	2

Frequencies

GnomAD3 genomes

AF:

0.574

AC:

87198

AN:

151994

Hom.:

25254

Cov.:

show subpopulations

Gnomad AFR

AF:

0.624

Gnomad AMI

AF:

0.649

Gnomad AMR

AF:

0.528

Gnomad ASJ

AF:

0.595

Gnomad EAS

AF:

0.565

Gnomad SAS

AF:

0.614

Gnomad FIN

AF:

0.537

Gnomad MID

AF:

0.595

Gnomad NFE

AF:

0.555

Gnomad OTH

AF:

0.565

GnomAD3 exomes

AF:

0.558

AC:

139540

AN:

250236

Hom.:

39388

AF XY:

0.560

AC XY:

75848

AN XY:

135324

show subpopulations

Gnomad AFR exome

AF:

0.631

Gnomad AMR exome

AF:

0.471

Gnomad ASJ exome

AF:

0.589

Gnomad EAS exome

AF:

0.590

Gnomad SAS exome

AF:

0.615

Gnomad FIN exome

AF:

0.535

Gnomad NFE exome

AF:

0.553

Gnomad OTH exome

AF:

0.572

GnomAD4 exome

AF:

0.551

AC:

784773

AN:

1424388

Hom.:

218453

Cov.:

AF XY:

0.553

AC XY:

393470

AN XY:

711018

show subpopulations

Gnomad4 AFR exome

AF:

0.630

Gnomad4 AMR exome

AF:

0.478

Gnomad4 ASJ exome

AF:

0.592

Gnomad4 EAS exome

AF:

0.596

Gnomad4 SAS exome

AF:

0.608

Gnomad4 FIN exome

AF:

0.545

Gnomad4 NFE exome

AF:

0.544

Gnomad4 OTH exome

AF:

0.562

GnomAD4 genome

AF:

0.574

AC:

87297

AN:

152112

Hom.:

25298

Cov.:

AF XY:

0.575

AC XY:

42786

AN XY:

74364

show subpopulations

Gnomad4 AFR

AF:

0.625

Gnomad4 AMR

AF:

0.528

Gnomad4 ASJ

AF:

0.595

Gnomad4 EAS

AF:

0.565

Gnomad4 SAS

AF:

0.613

Gnomad4 FIN

AF:

0.537

Gnomad4 NFE

AF:

0.555

Gnomad4 OTH

AF:

0.560

Alfa

AF:

0.548

Hom.:

16231

Bravo

AF:

0.575

TwinsUK

AF:

0.545

AC:

2022

ALSPAC

AF:

0.549

AC:

2116

ESP6500AA

AF:

0.622

AC:

2737

ESP6500EA

AF:

0.559

AC:

4808

ExAC

AF:

0.566

AC:

68718

Asia WGS

AF:

0.567

AC:

1970

AN:

3476

EpiCase

AF:

0.557

EpiControl

AF:

0.552

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.057

BayesDel_addAF

Benign

-0.73

BayesDel_noAF

Benign

-0.68

CADD

Benign

DANN

Benign

0.23

DEOGEN2

Benign

0.0031

Eigen

Benign

-0.63

Eigen_PC

Benign

-0.38

FATHMM_MKL

Benign

0.64

LIST_S2

Benign

0.033

MetaRNN

Benign

0.000058

MetaSVM

Benign

-1.0

PrimateAI

Benign

0.40

PROVEAN

Benign

0.52

REVEL

Benign

0.055

Sift

Benign

0.70

Sift4G

Benign

1.0

Polyphen

0.0

Vest4

0.051

MPC

0.0028

ClinPred

0.016

GERP RS

4.8

Varity_R

0.12

gMVP

0.59

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over