Genetic Variant NM_014303.4:c.1114C>G (chr22-30580108-G-C) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_014303.4(PES1):c.1114C>G(p.Arg372Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,824 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 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 variant affecting the same amino acid position, but resulting in a different missense (i.e. R372C) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

PES1
NM_014303.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.351

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:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.077142).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PES1	NM_014303.4 link	c.1114C>G	p.Arg372Gly	missense_variant	Exon 11 of 15	ENST00000354694.12	NP_055118.1	O00541-1B2RDF2
PES1	NM_001243225.2 link	c.1099C>G	p.Arg367Gly	missense_variant	Exon 11 of 15		NP_001230154.1	O00541-2
PES1	NM_001282327.1 link	c.697C>G	p.Arg233Gly	missense_variant	Exon 13 of 17		NP_001269256.1	F6VXF5
PES1	NM_001282328.1 link	c.697C>G	p.Arg233Gly	missense_variant	Exon 13 of 17		NP_001269257.1	F6VXF5B3KTZ6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PES1	ENST00000354694.12 link	c.1114C>G	p.Arg372Gly	missense_variant	Exon 11 of 15	1	NM_014303.4	ENSP00000346725.6		O00541-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461824

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727214

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33480

American (AMR)

AF:

0.00

AC:

AN:

44710

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26134

East Asian (EAS)

AF:

0.0000252

AC:

AN:

39700

South Asian (SAS)

AF:

0.00

AC:

AN:

86252

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53402

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1111986

Other (OTH)

AF:

0.00

AC:

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.064

BayesDel_addAF

Benign

-0.30

BayesDel_noAF

Benign

-0.67

CADD

Benign

1.3

(source)

DANN

Benign

0.96

DEOGEN2

Benign

0.18

T;.;.;T;.

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.14

LIST_S2

Uncertain

0.86

D;.;D;D;D

M_CAP

Benign

0.0059

MetaRNN

Benign

0.077

T;T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.2

L;.;.;.;.

PhyloP100

-0.35

PrimateAI

Benign

0.18

PROVEAN

Benign

-0.48

N;N;N;N;N

REVEL

Benign

0.096

Sift

Benign

0.044

D;D;D;D;D

Sift4G

Benign

0.11

T;T;T;T;T

Polyphen

0.035

B;.;.;B;B

Vest4

0.076

MutPred

0.56

Loss of stability (P = 0.0289);.;.;.;.;

MVP

0.25

MPC

0.31

ClinPred

0.14

GERP RS

-5.8

PromoterAI

0.0050

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.056

gMVP

0.25

Mutation Taster

=83/17

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.070

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over