Genetic Variant PUM3:p.Leu629Leu (chr9-2804393-A-G) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_014878.5(PUM3):c.1885T>C(p.Leu629Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0621 in 1,613,394 control chromosomes in the GnomAD database, including 4,311 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.092 ( 993 hom., cov: 32)

Exomes 𝑓: 0.059 ( 3318 hom. )

Consequence

PUM3
NM_014878.5 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.183

Publications

8 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:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BP7

Synonymous conserved (PhyloP=0.183 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.185 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PUM3	NM_014878.5 link	c.1885T>C	p.Leu629Leu	synonymous_variant	Exon 18 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.1885T>C	p.Leu629Leu	synonymous_variant	Exon 18 of 18	1	NM_014878.5	ENSP00000380982.2	Q15397
PUM3	ENST00000382032.3 link	n.232T>C		non_coding_transcript_exon_variant	Exon 2 of 2	2
PUM3	ENST00000490444.2 link	n.88T>C		non_coding_transcript_exon_variant	Exon 2 of 4	5		ENSP00000474467.1	S4R3K8

Frequencies

GnomAD3 genomes

AF:

0.0923

AC:

14028

AN:

152018

Hom.:

995

Cov.:

show subpopulations

Gnomad AFR

AF:

0.189

Gnomad AMI

AF:

0.0604

Gnomad AMR

AF:

0.0931

Gnomad ASJ

AF:

0.0413

Gnomad EAS

AF:

0.0556

Gnomad SAS

AF:

0.0877

Gnomad FIN

AF:

0.0442

Gnomad MID

AF:

0.0570

Gnomad NFE

AF:

0.0478

Gnomad OTH

AF:

0.0717

GnomAD2 exomes

AF:

0.0760

AC:

19085

AN:

251020

AF XY:

0.0724

show subpopulations

Gnomad AFR exome

AF:

0.194

Gnomad AMR exome

AF:

0.141

Gnomad ASJ exome

AF:

0.0459

Gnomad EAS exome

AF:

0.0477

Gnomad FIN exome

AF:

0.0457

Gnomad NFE exome

AF:

0.0479

Gnomad OTH exome

AF:

0.0650

GnomAD4 exome

AF:

0.0589

AC:

86100

AN:

1461258

Hom.:

3318

Cov.:

AF XY:

0.0592

AC XY:

43052

AN XY:

726902

show subpopulations

African (AFR)

AF:

0.192

AC:

6427

AN:

33438

American (AMR)

AF:

0.137

AC:

6113

AN:

44632

Ashkenazi Jewish (ASJ)

AF:

0.0479

AC:

1250

AN:

26120

East Asian (EAS)

AF:

0.0763

AC:

3027

AN:

39672

South Asian (SAS)

AF:

0.0970

AC:

8354

AN:

86090

European-Finnish (FIN)

AF:

0.0465

AC:

2480

AN:

53380

Middle Eastern (MID)

AF:

0.0618

AC:

356

AN:

5764

European-Non Finnish (NFE)

AF:

0.0488

AC:

54211

AN:

1111792

Other (OTH)

AF:

0.0643

AC:

3882

AN:

60370

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.481

Heterozygous variant carriers

3920

7839

11759

15678

19598

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0922

AC:

14026

AN:

152136

Hom.:

993

Cov.:

AF XY:

0.0903

AC XY:

6720

AN XY:

74396

show subpopulations

African (AFR)

AF:

0.188

AC:

7807

AN:

41472

American (AMR)

AF:

0.0931

AC:

1423

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.0413

AC:

143

AN:

3466

East Asian (EAS)

AF:

0.0559

AC:

289

AN:

5170

South Asian (SAS)

AF:

0.0880

AC:

424

AN:

4820

European-Finnish (FIN)

AF:

0.0442

AC:

468

AN:

10594

Middle Eastern (MID)

AF:

0.0578

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0478

AC:

3250

AN:

68004

Other (OTH)

AF:

0.0710

AC:

150

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

614

1229

1843

2458

3072

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0563

Hom.:

551

Bravo

AF:

0.102

Asia WGS

AF:

0.0920

AC:

317

AN:

3478

EpiCase

AF:

0.0491

EpiControl

AF:

0.0490

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

0.69

(source)

DANN

Benign

0.55

PhyloP100

0.18

Mutation Taster

=100/0

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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9-2804393-A-G

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