chr22-30579175-G-C

Position:

chr22-30579175-G-C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The ENST00000354694.12(PES1):c.1483C>G(p.Arg495Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00109 in 1,608,332 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00061 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0011 ( 1 hom. )

Consequence

PES1
ENST00000354694.12 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.404

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 made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.02326253).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
PES1	NM_014303.4 linkuse as main transcript	c.1483C>G	p.Arg495Gly	missense_variant	13/15	ENST00000354694.12	NP_055118.1
PES1	NM_001243225.2 linkuse as main transcript	c.1468C>G	p.Arg490Gly	missense_variant	13/15		NP_001230154.1
PES1	NM_001282327.1 linkuse as main transcript	c.1066C>G	p.Arg356Gly	missense_variant	15/17		NP_001269256.1
PES1	NM_001282328.1 linkuse as main transcript	c.1066C>G	p.Arg356Gly	missense_variant	15/17		NP_001269257.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PES1	ENST00000354694.12 linkuse as main transcript	c.1483C>G	p.Arg495Gly	missense_variant	13/15	1	NM_014303.4	ENSP00000346725	P3	O00541-1

Frequencies

GnomAD3 genomes

AF:

0.000611

AC:

AN:

152134

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000193

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000524

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000566

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00104

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000627

AC:

152

AN:

242298

Hom.:

AF XY:

0.000562

AC XY:

AN XY:

131612

show subpopulations

Gnomad AFR exome

AF:

0.0000632

Gnomad AMR exome

AF:

0.000876

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000547

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000489

Gnomad NFE exome

AF:

0.000961

Gnomad OTH exome

AF:

0.000999

GnomAD4 exome

AF:

0.00114

AC:

1657

AN:

1456080

Hom.:

Cov.:

AF XY:

0.00106

AC XY:

768

AN XY:

724590

show subpopulations

Gnomad4 AFR exome

AF:

0.000149

Gnomad4 AMR exome

AF:

0.000875

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.000329

Gnomad4 NFE exome

AF:

0.00140

Gnomad4 OTH exome

AF:

0.000580

GnomAD4 genome

AF:

0.000611

AC:

AN:

152252

Hom.:

Cov.:

AF XY:

0.000457

AC XY:

AN XY:

74460

show subpopulations

Gnomad4 AFR

AF:

0.000193

Gnomad4 AMR

AF:

0.000523

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000566

Gnomad4 NFE

AF:

0.00104

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000412

Hom.:

Bravo

AF:

0.000752

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.000519

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000930

AC:

ExAC

AF:

0.000527

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 02, 2024

The c.1483C>G (p.R495G) alteration is located in exon 13 (coding exon 13) of the PES1 gene. This alteration results from a C to G substitution at nucleotide position 1483, causing the arginine (R) at amino acid position 495 to be replaced by a glycine (G). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.52

BayesDel_noAF

Benign

-0.57

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.28

T;.;.;T;.

Eigen

Benign

-0.47

Eigen_PC

Benign

-0.42

FATHMM_MKL

Benign

0.37

LIST_S2

Benign

0.73

T;.;T;T;T

M_CAP

Benign

0.015

MetaRNN

Benign

0.023

T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.4

L;.;.;.;.

MutationTaster

Benign

1.0

N;N;N;N;N

PrimateAI

Benign

0.23

PROVEAN

Benign

-0.70

N;N;N;N;N

REVEL

Benign

0.077

Sift

Benign

0.38

T;T;T;T;T

Sift4G

Benign

0.35

T;T;T;T;T

Polyphen

0.011

B;.;.;B;B

Vest4

0.15

MVP

0.26

MPC

0.79

ClinPred

0.018

GERP RS

2.9

RBP_binding_hub_radar

0.97

RBP_regulation_power_radar

2.1

Varity_R

0.061

gMVP

0.096

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

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over