dbSNP rs2270891: PUM3:p.Val297Leu (chr9-2828742-C-A) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_014878.5(PUM3):c.889G>T(p.Val297Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0378 in 1,605,370 control chromosomes in the GnomAD database, including 1,348 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/19 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 the same amino acid substitution has been previously reported as Likely benign in UniProt.

Frequency

Genomes: 𝑓 0.043 ( 152 hom., cov: 33)

Exomes 𝑓: 0.037 ( 1196 hom. )

Consequence

PUM3
NM_014878.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.734

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:

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=0.0017007887).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0654 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PUM3	NM_014878.5 link	c.889G>T	p.Val297Leu	missense_variant	Exon 9 of 18	ENST00000397885.3	NP_055693.4	Q15397

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PUM3	ENST00000397885.3 link	c.889G>T	p.Val297Leu	missense_variant	Exon 9 of 18	1	NM_014878.5	ENSP00000380982.2		Q15397
PUM3	ENST00000469168.1 link	n.189G>T		non_coding_transcript_exon_variant	Exon 2 of 2	2

Frequencies

GnomAD3 genomes

AF:

0.0426

AC:

6488

AN:

152154

Hom.:

152

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0516

Gnomad AMI

AF:

0.0450

Gnomad AMR

AF:

0.0406

Gnomad ASJ

AF:

0.0383

Gnomad EAS

AF:

0.0712

Gnomad SAS

AF:

0.0340

Gnomad FIN

AF:

0.0383

Gnomad MID

AF:

0.0348

Gnomad NFE

AF:

0.0370

Gnomad OTH

AF:

0.0435

GnomAD3 exomes

AF:

0.0426

AC:

10687

AN:

250982

Hom.:

241

AF XY:

0.0411

AC XY:

5578

AN XY:

135652

show subpopulations

Gnomad AFR exome

AF:

0.0512

Gnomad AMR exome

AF:

0.0557

Gnomad ASJ exome

AF:

0.0387

Gnomad EAS exome

AF:

0.0604

Gnomad SAS exome

AF:

0.0377

Gnomad FIN exome

AF:

0.0402

Gnomad NFE exome

AF:

0.0365

Gnomad OTH exome

AF:

0.0435

GnomAD4 exome

AF:

0.0373

AC:

54180

AN:

1453098

Hom.:

1196

Cov.:

AF XY:

0.0373

AC XY:

26982

AN XY:

723512

show subpopulations

Gnomad4 AFR exome

AF:

0.0474

Gnomad4 AMR exome

AF:

0.0548

Gnomad4 ASJ exome

AF:

0.0379

Gnomad4 EAS exome

AF:

0.101

Gnomad4 SAS exome

AF:

0.0355

Gnomad4 FIN exome

AF:

0.0402

Gnomad4 NFE exome

AF:

0.0339

Gnomad4 OTH exome

AF:

0.0375

GnomAD4 genome

AF:

0.0426

AC:

6491

AN:

152272

Hom.:

152

Cov.:

AF XY:

0.0420

AC XY:

3128

AN XY:

74456

show subpopulations

Gnomad4 AFR

AF:

0.0514

Gnomad4 AMR

AF:

0.0406

Gnomad4 ASJ

AF:

0.0383

Gnomad4 EAS

AF:

0.0713

Gnomad4 SAS

AF:

0.0340

Gnomad4 FIN

AF:

0.0383

Gnomad4 NFE

AF:

0.0370

Gnomad4 OTH

AF:

0.0435

Alfa

AF:

0.0376

Hom.:

208

Bravo

AF:

0.0439

TwinsUK

AF:

0.0264

AC:

ALSPAC

AF:

0.0317

AC:

122

ESP6500AA

AF:

0.0495

AC:

218

ESP6500EA

AF:

0.0397

AC:

341

ExAC

AF:

0.0431

AC:

5231

Asia WGS

AF:

0.0600

AC:

210

AN:

3478

EpiCase

AF:

0.0384

EpiControl

AF:

0.0366

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.080

BayesDel_addAF

Benign

-0.77

BayesDel_noAF

Benign

-0.76

CADD

Benign

8.1

DANN

Benign

0.96

DEOGEN2

Benign

0.0026

Eigen

Benign

-0.77

Eigen_PC

Benign

-0.69

FATHMM_MKL

Benign

0.69

LIST_S2

Benign

0.46

MetaRNN

Benign

0.0017

MetaSVM

Benign

-0.96

PrimateAI

Benign

0.30

PROVEAN

Benign

-0.64

REVEL

Benign

0.060

Sift

Benign

0.34

Sift4G

Benign

0.26

Polyphen

0.0

Vest4

0.030

MutPred

0.097

Loss of ubiquitination at K293 (P = 0.0834);

MPC

0.0035

ClinPred

0.0013

GERP RS

0.67

Varity_R

0.075

gMVP

0.39

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