Genetic Variant NM_014303.4:c.1725G>A (chr22-30577088-C-T) – ACMG Classification: Benign (-11 pts)

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_014303.4(PES1):c.1725G>A(p.Ala575Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000433 in 1,614,136 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0023 ( 1 hom., cov: 33)

Exomes 𝑓: 0.00024 ( 4 hom. )

Consequence

PES1
NM_014303.4 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.02

Publications

0 publications found

Variant links:

Genes affected

PES1 (HGNC:8848): (pescadillo ribosomal biogenesis factor 1) This gene encodes a nuclear protein that contains a breast cancer associated gene 1 (BRCA1) C-terminal interaction domain. The encoded protein interacts with BOP1 and WDR12 to form the PeBoW complex, which plays a critical role in cell proliferation via pre-rRNA processing and 60S ribosomal subunit maturation. Expression of this gene may play an important role in breast cancer proliferation and tumorigenicity. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. Pseudogenes of this gene are located on the long arm of chromosome 4 and the short arm of chromosome 9. [provided by RefSeq, Aug 2011]

PES1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -11 ACMG points.

BP4

Computational evidence support a benign effect (REVEL=0.011).

BP6

Variant 22-30577088-C-T is Benign according to our data. Variant chr22-30577088-C-T is described in ClinVar as [Benign]. Clinvar id is 717123.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-1.02 with no splicing effect.

BS2

High Homozygotes in GnomAdExome4 at 4 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PES1	NM_014303.4 link	c.1725G>A	p.Ala575Ala	synonymous_variant	Exon 15 of 15	ENST00000354694.12	NP_055118.1	O00541-1B2RDF2
PES1	NM_001243225.2 link	c.1710G>A	p.Ala570Ala	synonymous_variant	Exon 15 of 15		NP_001230154.1	O00541-2
PES1	NM_001282327.1 link	c.1308G>A	p.Ala436Ala	synonymous_variant	Exon 17 of 17		NP_001269256.1	F6VXF5
PES1	NM_001282328.1 link	c.1308G>A	p.Ala436Ala	synonymous_variant	Exon 17 of 17		NP_001269257.1	F6VXF5B3KTZ6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PES1	ENST00000354694.12 link	c.1725G>A	p.Ala575Ala	synonymous_variant	Exon 15 of 15	1	NM_014303.4	ENSP00000346725.6		O00541-1

Frequencies

GnomAD3 genomes

AF:

0.00225

AC:

342

AN:

152206

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00748

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00150

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00287

GnomAD2 exomes

AF:

0.000689

AC:

173

AN:

251214

AF XY:

0.000456

show subpopulations

Gnomad AFR exome

AF:

0.00819

Gnomad AMR exome

AF:

0.000925

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000881

Gnomad OTH exome

AF:

0.00114

GnomAD4 exome

AF:

0.000243

AC:

355

AN:

1461812

Hom.:

Cov.:

AF XY:

0.000193

AC XY:

140

AN XY:

727216

show subpopulations

African (AFR)

AF:

0.00789

AC:

264

AN:

33478

American (AMR)

AF:

0.000984

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.000101

AC:

AN:

39700

South Asian (SAS)

AF:

0.0000580

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53354

Middle Eastern (MID)

AF:

0.000694

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

0.00000629

AC:

AN:

1112002

Other (OTH)

AF:

0.000447

AC:

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.466

Heterozygous variant carriers

106

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.00226

AC:

344

AN:

152324

Hom.:

Cov.:

AF XY:

0.00215

AC XY:

160

AN XY:

74486

show subpopulations

African (AFR)

AF:

0.00750

AC:

312

AN:

41582

American (AMR)

AF:

0.00150

AC:

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5180

South Asian (SAS)

AF:

0.000207

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10616

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000294

AC:

AN:

68028

Other (OTH)

AF:

0.00284

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.000769

Hom.:

Bravo

AF:

0.00249

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

May 08, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.72

CADD

Benign

6.0

(source)

DANN

Benign

0.78

PhyloP100

-1.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Mutation Taster

=100/0

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

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NM_014303.4:c.1725G>A

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over