4-765023-C-T

Variant names:

• chr4-765023-C-T
• rs1745284197
• NM_006315.7:c.640C>T

Variant summary

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

The NM_006315.7(PCGF3):​c.640C>T​(p.His214Tyr) variant causes a missense change involving the alteration of a 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: PCGF3 NM_006315.7 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.24
• Publications: 0 publications found

Genes affected

PCGF3 (HGNC:10066): (polycomb group ring finger 3) The protein encoded by this gene contains a C3HC4 type RING finger, which is a motif known to be involved in protein-protein interactions. The specific function of this protein has not yet been determined. [provided by RefSeq, Jul 2008]

LOC124900163 (HGNC:):

PCGF3-AS1 (HGNC:56108): (PCGF3 antisense RNA 1)

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, 0.824

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006315.7. 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
	PCGF3	NM_006315.7	MANE Select	c.640C>T	p.His214Tyr	missense	Exon 10 of 11	NP_006306.2
	PCGF3	NM_001317836.3		c.640C>T	p.His214Tyr	missense	Exon 11 of 12	NP_001304765.1	Q3KNV8-1
	PCGF3	NM_001395245.1		c.640C>T	p.His214Tyr	missense	Exon 11 of 12	NP_001382174.1	Q3KNV8-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PCGF3	ENST00000362003.10	TSL:5 MANE Select	c.640C>T	p.His214Tyr	missense	Exon 10 of 11	ENSP00000354724.5	Q3KNV8-1
	PCGF3	ENST00000470161.6	TSL:1	c.640C>T	p.His214Tyr	missense	Exon 10 of 11	ENSP00000420489.2	Q3KNV8-1
	PCGF3	ENST00000870362.1		c.640C>T	p.His214Tyr	missense	Exon 11 of 12	ENSP00000540421.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	See cases (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.99
BayesDel_addAF	Pathogenic	0.19	D
BayesDel_noAF	Uncertain	0.040
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.53	D
Eigen	Uncertain	0.29
Eigen_PC	Uncertain	0.38
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Uncertain	0.96	D
M_CAP	Benign	0.016	T
MetaRNN	Pathogenic	0.82	D
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.89	L
PhyloP100		7.2
PrimateAI	Pathogenic	0.89	D
PROVEAN	Uncertain	-3.9	D
REVEL	Uncertain	0.34
Sift	Benign	0.057	T
Sift4G	Benign	0.31	T
Polyphen		1.0	D
Vest4		0.87
MutPred		0.60		Loss of methylation at K217 (P = 0.0448)
MVP		0.55
MPC		2.1
ClinPred		0.98	D
GERP RS		5.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.59
gMVP		0.93
Mutation Taster		=49/51	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs1745284197; hg19: chr4-758811;