chr22-30581027-C-G

Variant names:

• chr22-30581027-C-G
• rs2108110
• NM_014303.4:c.897G>C

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_014303.4(PES1):​c.897G>C​(p.Glu299Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000491 in 1,612,610 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00036 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00050 (0 hom.)
• Consequence: PES1 NM_014303.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.460
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.032566905).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014303.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PES1	NM_014303.4	MANE Select	c.897G>C	p.Glu299Asp	missense	Exon 9 of 15	NP_055118.1	B2RDF2
	PES1	NM_001243225.2		c.897G>C	p.Glu299Asp	missense	Exon 9 of 15	NP_001230154.1	O00541-2
	PES1	NM_001282327.1		c.480G>C	p.Glu160Asp	missense	Exon 11 of 17	NP_001269256.1	F6VXF5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PES1	ENST00000354694.12	TSL:1 MANE Select	c.897G>C	p.Glu299Asp	missense	Exon 9 of 15	ENSP00000346725.6	O00541-1
	PES1	ENST00000335214.8	TSL:1	c.897G>C	p.Glu299Asp	missense	Exon 9 of 15	ENSP00000334612.6	O00541-2
	PES1	ENST00000898785.1		c.915G>C	p.Glu305Asp	missense	Exon 9 of 15	ENSP00000568844.1

Frequencies

GnomAD3 genomes AF: 0.000361 AC: 55 AN: 152242 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000482

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000131

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.0000941

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000705

Gnomad OTH AF: 0.000478

GnomAD2 exomes AF: 0.000479 AC: 119 AN: 248476 AF XY: 0.000482

Gnomad AFR exome AF: 0.0000626

Gnomad AMR exome AF: 0.000407

Gnomad ASJ exome AF: 0.000201

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000814

Gnomad OTH exome AF: 0.00149

GnomAD4 exome AF: 0.000505 AC: 737 AN: 1460250 Hom.: 0 Cov.: 32 AF XY: 0.000496 AC XY: 360 AN XY: 726428

African (AFR) AF: 0.0000896 AC: 3 AN: 33464

American (AMR) AF: 0.000336 AC: 15 AN: 44632

Ashkenazi Jewish (ASJ) AF: 0.0000766 AC: 2 AN: 26122

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.0000232 AC: 2 AN: 86138

European-Finnish (FIN) AF: 0.0000571 AC: 3 AN: 52562

Middle Eastern (MID) AF: 0.000694 AC: 4 AN: 5762

European-Non Finnish (NFE) AF: 0.000615 AC: 684 AN: 1111536

Other (OTH) AF: 0.000398 AC: 24 AN: 60336

GnomAD4 genome AF: 0.000361 AC: 55 AN: 152360 Hom.: 0 Cov.: 33 AF XY: 0.000255 AC XY: 19 AN XY: 74496

African (AFR) AF: 0.0000481 AC: 2 AN: 41592

American (AMR) AF: 0.000131 AC: 2 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4828

European-Finnish (FIN) AF: 0.0000941 AC: 1 AN: 10626

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000706 AC: 48 AN: 68032

Other (OTH) AF: 0.000473 AC: 1 AN: 2114

Alfa AF: 0.000381 Hom.: 0

Bravo AF: 0.000374

TwinsUK AF: 0.000809 AC: 3

ALSPAC AF: 0.000259 AC: 1

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000349 AC: 3

ExAC AF: 0.000495 AC: 60

EpiCase AF: 0.00109

EpiControl AF: 0.00113

ClinVar

ClinVar submissions as Germline

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.52	T
BayesDel_noAF	Benign	-0.58
CADD	Benign	10
DANN	Benign	0.96
DEOGEN2	Uncertain	0.44	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.54	D
LIST_S2	Benign	0.77	T
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.033	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.2	M
PhyloP100		-0.46
PrimateAI	Benign	0.39	T
PROVEAN	Benign	-1.4	N
REVEL	Benign	0.016
Sift	Benign	0.13	T
Sift4G	Benign	0.13	T
Polyphen		0.031	B
Vest4		0.32
MutPred		0.19		Loss of helix (P = 0.1299)
MVP		0.30
MPC		0.32
ClinPred		0.012	T
GERP RS		-3.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.043
gMVP		0.16
Mutation Taster		=83/17	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs2108110; hg19: chr22-30977014;