dbSNP rs10968457: PUM3:p.Ser13Asn (chr9-2838470-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_014878.5(PUM3):c.38G>A(p.Ser13Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0371 in 1,612,134 control chromosomes in the GnomAD database, including 1,282 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.035 ( 104 hom., cov: 32)

Exomes 𝑓: 0.037 ( 1178 hom. )

Consequence

PUM3
NM_014878.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0410

Publications

17 publications found

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:

ENSG00000290482 (HGNC:):

ENSG00000290482 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0013602376).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0572 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PUM3	NM_014878.5 link	c.38G>A	p.Ser13Asn	missense_variant	Exon 2 of 18	ENST00000397885.3	NP_055693.4	Q15397

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
PUM3	ENST00000397885.3 link	c.38G>A	p.Ser13Asn	missense_variant	Exon 2 of 18	1	NM_014878.5	ENSP00000380982.2	Q15397
ENSG00000290482	ENST00000716558.1 link	n.877G>A		non_coding_transcript_exon_variant	Exon 6 of 8
ENSG00000290482	ENST00000716559.1 link	n.1125G>A		non_coding_transcript_exon_variant	Exon 7 of 9
ENSG00000290482	ENST00000716560.1 link	n.1403G>A		non_coding_transcript_exon_variant	Exon 8 of 8

Frequencies

GnomAD3 genomes

AF:

0.0350

AC:

5328

AN:

152096

Hom.:

104

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0250

Gnomad AMI

AF:

0.0451

Gnomad AMR

AF:

0.0386

Gnomad ASJ

AF:

0.0389

Gnomad EAS

AF:

0.0627

Gnomad SAS

AF:

0.0317

Gnomad FIN

AF:

0.0388

Gnomad MID

AF:

0.0348

Gnomad NFE

AF:

0.0375

Gnomad OTH

AF:

0.0365

GnomAD2 exomes

AF:

0.0404

AC:

10060

AN:

249140

AF XY:

0.0398

show subpopulations

Gnomad AFR exome

AF:

0.0241

Gnomad AMR exome

AF:

0.0532

Gnomad ASJ exome

AF:

0.0399

Gnomad EAS exome

AF:

0.0545

Gnomad FIN exome

AF:

0.0404

Gnomad NFE exome

AF:

0.0371

Gnomad OTH exome

AF:

0.0427

GnomAD4 exome

AF:

0.0373

AC:

54476

AN:

1459920

Hom.:

1178

Cov.:

AF XY:

0.0374

AC XY:

27133

AN XY:

726382

show subpopulations

African (AFR)

AF:

0.0228

AC:

761

AN:

33436

American (AMR)

AF:

0.0527

AC:

2353

AN:

44632

Ashkenazi Jewish (ASJ)

AF:

0.0392

AC:

1023

AN:

26082

East Asian (EAS)

AF:

0.0895

AC:

3548

AN:

39622

South Asian (SAS)

AF:

0.0354

AC:

3051

AN:

86140

European-Finnish (FIN)

AF:

0.0404

AC:

2156

AN:

53384

Middle Eastern (MID)

AF:

0.0488

AC:

281

AN:

5762

European-Non Finnish (NFE)

AF:

0.0352

AC:

39101

AN:

1110528

Other (OTH)

AF:

0.0365

AC:

2202

AN:

60334

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.432

Heterozygous variant carriers

2459

4919

7378

9838

12297

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1504

3008

4512

6016

7520

<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

AF:

0.0350

AC:

5333

AN:

152214

Hom.:

104

Cov.:

AF XY:

0.0343

AC XY:

2554

AN XY:

74420

show subpopulations

African (AFR)

AF:

0.0250

AC:

1039

AN:

41540

American (AMR)

AF:

0.0386

AC:

590

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.0389

AC:

135

AN:

3470

East Asian (EAS)

AF:

0.0629

AC:

326

AN:

5186

South Asian (SAS)

AF:

0.0318

AC:

153

AN:

4818

European-Finnish (FIN)

AF:

0.0388

AC:

411

AN:

10606

Middle Eastern (MID)

AF:

0.0306

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0375

AC:

2550

AN:

67996

Other (OTH)

AF:

0.0375

AC:

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

266

532

797

1063

1329

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

124

186

248

310

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0379

Hom.:

557

Bravo

AF:

0.0355

TwinsUK

AF:

0.0259

AC:

ALSPAC

AF:

0.0311

AC:

120

ESP6500AA

AF:

0.0260

AC:

ESP6500EA

AF:

0.0411

AC:

337

ExAC

AF:

0.0405

AC:

4898

Asia WGS

AF:

0.0550

AC:

191

AN:

3478

EpiCase

AF:

0.0381

EpiControl

AF:

0.0371

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.057

BayesDel_addAF

Benign

-0.60

BayesDel_noAF

Benign

-0.54

CADD

Benign

1.4

(source)

DANN

Benign

0.73

DEOGEN2

Benign

0.0059

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.10

LIST_S2

Benign

0.44

MetaRNN

Benign

0.0014

MetaSVM

Benign

-1.0

PhyloP100

0.041

PrimateAI

Benign

0.30

PROVEAN

Benign

-0.090

REVEL

Benign

0.24

Sift

Benign

0.55

Sift4G

Benign

1.0

Polyphen

0.0

Vest4

0.017

MPC

0.0036

ClinPred

0.00092

GERP RS

-1.5

Varity_R

0.031

gMVP

0.038

Mutation Taster

=95/5

polymorphism (auto)

(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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over