chr22-30579762-C-T

Variant names:

• chr22-30579762-C-T
• rs1035694104
• NM_014303.4:c.1343G>A

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_014303.4(PES1):​c.1343G>A​(p.Gly448Glu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: PES1 NM_014303.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.86
• Publications: 2 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: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.1343G>A	p.Gly448Glu	missense	Exon 12 of 15	NP_055118.1	B2RDF2
	PES1	NM_001243225.2		c.1328G>A	p.Gly443Glu	missense	Exon 12 of 15	NP_001230154.1	O00541-2
	PES1	NM_001282327.1		c.926G>A	p.Gly309Glu	missense	Exon 14 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.1343G>A	p.Gly448Glu	missense	Exon 12 of 15	ENSP00000346725.6	O00541-1
	PES1	ENST00000335214.8	TSL:1	c.1328G>A	p.Gly443Glu	missense	Exon 12 of 15	ENSP00000334612.6	O00541-2
	PES1	ENST00000898785.1		c.1346G>A	p.Gly449Glu	missense	Exon 12 of 15	ENSP00000568844.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

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	Uncertain	0.49
BayesDel_addAF	Uncertain	0.10	D
BayesDel_noAF	Benign	-0.090
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.42	T
Eigen	Uncertain	0.57
Eigen_PC	Uncertain	0.58
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.94	D
M_CAP	Benign	0.029	D
MetaRNN	Uncertain	0.60	D
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.6	M
PhyloP100		7.9
PrimateAI	Uncertain	0.71	T
PROVEAN	Benign	-1.7	N
REVEL	Benign	0.20
Sift	Benign	0.053	T
Sift4G	Benign	0.14	T
Polyphen		1.0	D
Vest4		0.71
MutPred		0.15		Gain of helix (P = 0.027)
MVP		0.33
MPC		1.0
ClinPred		0.95	D
GERP RS		4.9
PromoterAI		0.033	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.33
gMVP		0.52
Mutation Taster		=18/82	disease causing

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

Other links and lift over

dbSNP: rs1035694104; hg19: chr22-30975749; COSMIC: COSV58828561; COSMIC: COSV58828561;