22-30580691-G-C

Variant names:

• chr22-30580691-G-C
• NM_014303.4:c.923C>G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_014303.4(PES1):​c.923C>G​(p.Ala308Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: PES1 NM_014303.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.209

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

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=0.06528637).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PES1	NM_014303.4	c.923C>G	p.Ala308Gly	missense_variant	Exon 10 of 15	ENST00000354694.12	NP_055118.1
PES1	NM_001282327.1	c.506C>G	p.Ala169Gly	missense_variant	Exon 12 of 17		NP_001269256.1
PES1	NM_001282328.1	c.506C>G	p.Ala169Gly	missense_variant	Exon 12 of 17		NP_001269257.1
PES1	NM_001243225.2	c.913-5C>G		splice_region_variant, intron_variant	Intron 9 of 14		NP_001230154.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PES1	ENST00000354694.12	c.923C>G	p.Ala308Gly	missense_variant	Exon 10 of 15	1	NM_014303.4	ENSP00000346725.6

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.082
BayesDel_addAF	Benign	-0.33	T
BayesDel_noAF	Benign	-0.71
CADD	Benign	5.3
DANN	Benign	0.65
DEOGEN2	Benign	0.38	T;.;.;T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.26	N
LIST_S2	Benign	0.62	T;.;T;T
M_CAP	Benign	0.0045	T
MetaRNN	Benign	0.065	T;T;T;T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	1.2	L;.;.;.
PrimateAI	Benign	0.26	T
PROVEAN	Benign	-0.54	N;N;N;N
REVEL	Benign	0.014
Sift	Benign	0.28	T;T;T;T
Sift4G	Benign	0.35	T;T;T;T
Polyphen		0.0080	B;.;.;B
Vest4		0.19
MutPred		0.23		Gain of glycosylation at S307 (P = 0.0427);.;.;.;
MVP		0.25
MPC		0.26
ClinPred		0.056	T
GERP RS		-3.7
Varity_R		0.034
gMVP		0.15

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr22-30976678;