2-74506877-C-A

Variant names:

• chr2-74506877-C-A
• NM_032673.3:c.207G>T

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_032673.3(PCGF1):​c.207G>T​(p.Lys69Asn) 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 pathogenic 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: 0.563
• 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 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.776

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.207G>T	p.Lys69Asn	missense	Exon 3 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.207G>T	p.Lys69Asn	missense	Exon 3 of 9	ENSP00000233630.6	Q9BSM1-1
	PCGF1	ENST00000475863.5	TSL:1	n.383G>T		non_coding_transcript_exon	Exon 2 of 8
	PCGF1	ENST00000877061.1		c.246G>T	p.Lys82Asn	missense	Exon 3 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	Pathogenic	1.0
BayesDel_addAF	Benign	-0.091	T
BayesDel_noAF	Benign	-0.37
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.20	T
Eigen	Benign	0.13
Eigen_PC	Benign	0.041
FATHMM_MKL	Benign	0.49	N
LIST_S2	Uncertain	0.93	D
M_CAP	Benign	0.041	D
MetaRNN	Pathogenic	0.78	D
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.2	M
PhyloP100		0.56
PrimateAI	Pathogenic	0.92	D
PROVEAN	Pathogenic	-4.6	D
REVEL	Benign	0.23
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.0020	D
Polyphen		1.0	D
Vest4		0.76
MutPred		0.66		Loss of methylation at K69 (P = 8e-04)
MVP		0.39
MPC		2.1
ClinPred		1.0	D
GERP RS		0.59
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.7
Varity_R		0.86
gMVP		0.93
Mutation Taster		=53/47	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: chr2-74734004;