NM_006315.7:c.523C>A

Variant names:

• chr4-761339-C-A
• rs1318646361
• NM_006315.7:c.523C>A

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_006315.7(PCGF3):​c.523C>A​(p.Arg175Ser) variant causes a missense change. The variant allele was found at a frequency of 0.000000686 in 1,458,584 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R175C) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: PCGF3 NM_006315.7 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.36
• 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 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.93

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.523C>A	p.Arg175Ser	missense	Exon 9 of 11	NP_006306.2
	PCGF3	NM_001317836.3		c.523C>A	p.Arg175Ser	missense	Exon 10 of 12	NP_001304765.1	Q3KNV8-1
	PCGF3	NM_001395245.1		c.523C>A	p.Arg175Ser	missense	Exon 10 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.523C>A	p.Arg175Ser	missense	Exon 9 of 11	ENSP00000354724.5	Q3KNV8-1
	PCGF3	ENST00000470161.6	TSL:1	c.523C>A	p.Arg175Ser	missense	Exon 9 of 11	ENSP00000420489.2	Q3KNV8-1
	PCGF3	ENST00000870362.1		c.523C>A	p.Arg175Ser	missense	Exon 10 of 12	ENSP00000540421.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.86e-7 AC: 1 AN: 1458584 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 725158

African (AFR) AF: 0.00 AC: 0 AN: 33380

American (AMR) AF: 0.00 AC: 0 AN: 44308

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26086

East Asian (EAS) AF: 0.00 AC: 0 AN: 39592

South Asian (SAS) AF: 0.00 AC: 0 AN: 85728

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53278

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5760

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1110160

Other (OTH) AF: 0.0000166 AC: 1 AN: 60292

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	1.0
BayesDel_addAF	Pathogenic	0.29	D
BayesDel_noAF	Pathogenic	0.18
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.74	D
Eigen	Uncertain	0.64
Eigen_PC	Uncertain	0.55
FATHMM_MKL	Uncertain	0.85	D
LIST_S2	Pathogenic	0.98	D
M_CAP	Benign	0.071	D
MetaRNN	Pathogenic	0.93	D
MetaSVM	Benign	-0.32	T
MutationAssessor	Pathogenic	3.0	M
PhyloP100		5.4
PrimateAI	Pathogenic	0.81	D
PROVEAN	Pathogenic	-5.4	D
REVEL	Uncertain	0.49
Sift	Uncertain	0.0020	D
Sift4G	Uncertain	0.0030	D
Polyphen		1.0	D
Vest4		0.88
MutPred		0.78		Loss of MoRF binding (P = 0.0662)
MVP		0.80
MPC		2.0
ClinPred		0.99	D
GERP RS		4.1
Varity_R		0.90
gMVP		0.91
Mutation Taster		=48/52	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: rs1318646361; hg19: chr4-755127;