chr2-74506848-C-T

Variant names:

• chr2-74506848-C-T
• rs1665808070
• NM_032673.3:c.236G>A

Variant summary

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

The NM_032673.3(PCGF1):​c.236G>A​(p.Ser79Asn) variant causes a missense change. 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: 4.62
• 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.236G>A	p.Ser79Asn	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.236G>A	p.Ser79Asn	missense	Exon 3 of 9	ENSP00000233630.6	Q9BSM1-1
	PCGF1	ENST00000475863.5	TSL:1	n.412G>A		non_coding_transcript_exon	Exon 2 of 8
	PCGF1	ENST00000877061.1		c.275G>A	p.Ser92Asn	missense	Exon 3 of 9	ENSP00000547120.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

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	0.84
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.50
CADD	Pathogenic	27
DANN	Benign	0.97
DEOGEN2	Benign	0.057	T
Eigen	Uncertain	0.39
Eigen_PC	Uncertain	0.48
FATHMM_MKL	Benign	0.74	D
LIST_S2	Benign	0.84	T
M_CAP	Benign	0.010	T
MetaRNN	Uncertain	0.69	D
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.52	N
PhyloP100		4.6
PrimateAI	Pathogenic	0.90	D
PROVEAN	Benign	-0.34	N
REVEL	Benign	0.25
Sift	Benign	0.45	T
Sift4G	Benign	0.46	T
Polyphen		1.0	D
Vest4		0.63
MutPred		0.47		Loss of catalytic residue at S79 (P = 0.0829)
MVP		0.44
MPC		1.3
ClinPred		0.65	D
GERP RS		5.7
Varity_R		0.25
gMVP		0.72
Mutation Taster		=57/43	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.16		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: rs1665808070; hg19: chr2-74733975;