2-74506211-A-C

Variant names:

• chr2-74506211-A-C
• NM_032673.3:c.394T>G

Variant summary

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

The NM_032673.3(PCGF1):​c.394T>G​(p.Leu132Val) variant causes a missense change involving the alteration of a non-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: PCGF1 NM_032673.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.62
• 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 2 ACMG points.

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

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.394T>G	p.Leu132Val	missense	Exon 4 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.394T>G	p.Leu132Val	missense	Exon 4 of 9	ENSP00000233630.6	Q9BSM1-1
	PCGF1	ENST00000475863.5	TSL:1	n.570T>G		non_coding_transcript_exon	Exon 3 of 8
	PCGF1	ENST00000877061.1		c.433T>G	p.Leu145Val	missense	Exon 4 of 9	ENSP00000547120.1

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	0.37
BayesDel_addAF	Benign	-0.089	T
BayesDel_noAF	Benign	-0.37
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.066	T
Eigen	Uncertain	0.25
Eigen_PC	Benign	0.21
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.92	D
M_CAP	Benign	0.013	T
MetaRNN	Uncertain	0.46	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Uncertain	2.1	M
PhyloP100		1.6
PrimateAI	Uncertain	0.69	T
PROVEAN	Benign	-1.4	N
REVEL	Benign	0.15
Sift	Benign	0.19	T
Sift4G	Benign	0.23	T
Polyphen		0.99	D
Vest4		0.49
MutPred		0.22		Loss of stability (P = 0.0897)
MVP		0.66
MPC		1.6
ClinPred		0.88	D
GERP RS		1.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.11
gMVP		0.39
Mutation Taster		=82/18	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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

hg19: chr2-74733338;