NM_014303.4:c.923C>G

Variant names:

• chr22-30580691-G-C
• rs149639037
• NM_014303.4:c.923C>G

Variant summary

Our verdict is Likely benign. The variant received -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. 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. A308V) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: PES1 NM_014303.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.209
• 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 -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.06528637).

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.923C>G	p.Ala308Gly	missense	Exon 10 of 15	NP_055118.1	B2RDF2
	PES1	NM_001282327.1		c.506C>G	p.Ala169Gly	missense	Exon 12 of 17	NP_001269256.1	F6VXF5
	PES1	NM_001282328.1		c.506C>G	p.Ala169Gly	missense	Exon 12 of 17	NP_001269257.1	B3KTZ6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PES1	ENST00000354694.12	TSL:1 MANE Select	c.923C>G	p.Ala308Gly	missense	Exon 10 of 15	ENSP00000346725.6	O00541-1
	PES1	ENST00000335214.8	TSL:1	c.913-5C>G		splice_region intron	N/A	ENSP00000334612.6	O00541-2
	PES1	ENST00000898784.1		c.920C>G	p.Ala307Gly	missense	Exon 10 of 15	ENSP00000568843.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

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
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.26	N
LIST_S2	Benign	0.62	T
M_CAP	Benign	0.0045	T
MetaRNN	Benign	0.065	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	1.2	L
PhyloP100		0.21
PrimateAI	Benign	0.26	T
PROVEAN	Benign	-0.54	N
REVEL	Benign	0.014
Sift	Benign	0.28	T
Sift4G	Benign	0.35	T
Polyphen		0.0080	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
Mutation Taster		=95/5	polymorphism

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

Other links and lift over

dbSNP: rs149639037; hg19: chr22-30976678;