2-74507142-C-A

Variant names:

• chr2-74507142-C-A
• rs766403843
• NM_032673.3:c.99G>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_032673.3(PCGF1):​c.99G>T​(p.Glu33Asp) 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. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: PCGF1 NM_032673.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.542
• Publications: 0 publications found

Genes affected

PCGF1 (HGNC:17615): (polycomb group ring finger 1) PCGF1 is a mammalian homolog of the Drosophila polycomb group genes, which act as transcriptional repressors to regulate anterior-posterior patterning in early embryonic development (Nunes et al., 2001 [PubMed 11287196]). See also PCGF2 (MIM 600346).[supplied by OMIM, Aug 2008]

ACMG classification

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=0.0705007).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032673.3. 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
	PCGF1	NM_032673.3	MANE Select	c.99G>T	p.Glu33Asp	missense	Exon 2 of 9	NP_116062.2	Q9BSM1-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PCGF1	ENST00000233630.11	TSL:1 MANE Select	c.99G>T	p.Glu33Asp	missense	Exon 2 of 9	ENSP00000233630.6	Q9BSM1-1
	PCGF1	ENST00000475863.5	TSL:1	n.275G>T		non_coding_transcript_exon	Exon 1 of 8
	PCGF1	ENST00000877061.1		c.138G>T	p.Glu46Asp	missense	Exon 2 of 9	ENSP00000547120.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

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	Benign	0.25
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	18
DANN	Benign	0.96
DEOGEN2	Benign	0.050	T
Eigen	Benign	-0.90
Eigen_PC	Benign	-0.72
FATHMM_MKL	Benign	0.29	N
LIST_S2	Uncertain	0.90	D
M_CAP	Benign	0.0090	T
MetaRNN	Benign	0.071	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N
PhyloP100		0.54
PrimateAI	Uncertain	0.76	T
PROVEAN	Benign	-1.2	N
REVEL	Benign	0.073
Sift	Benign	0.20	T
Sift4G	Benign	0.30	T
Polyphen		0.038	B
Vest4		0.27
MutPred		0.30		Loss of methylation at K37 (P = 0.1294)
MVP		0.082
MPC		0.76
ClinPred		0.13	T
GERP RS		1.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.17
gMVP		0.79
Mutation Taster		=72/28	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: rs766403843; hg19: chr2-74734269;