rs2242234

Variant names:

• chr4-761341-C-T
• rs2242234
• NM_006315.7:c.525C>T
• PCGF3 p.Arg175Arg

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Moderate BP7 BA1

The NM_006315.7(PCGF3):​c.525C>T​(p.Arg175Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0598 in 1,610,694 control chromosomes in the GnomAD database, including 3,446 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.051 (286 hom., cov: 33)
  • Exomes 𝑓: 0.061 (3160 hom.)
• Consequence: PCGF3 NM_006315.7 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.01
• Publications: 15 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: Benign. The variant received -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.46).
• BP7: Synonymous conserved (PhyloP=1.01 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.114 is higher than 0.05.

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.525C>T	p.Arg175Arg	synonymous	Exon 9 of 11	NP_006306.2
	PCGF3	NM_001317836.3		c.525C>T	p.Arg175Arg	synonymous	Exon 10 of 12	NP_001304765.1	Q3KNV8-1
	PCGF3	NM_001395245.1		c.525C>T	p.Arg175Arg	synonymous	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.525C>T	p.Arg175Arg	synonymous	Exon 9 of 11	ENSP00000354724.5	Q3KNV8-1
	PCGF3	ENST00000470161.6	TSL:1	c.525C>T	p.Arg175Arg	synonymous	Exon 9 of 11	ENSP00000420489.2	Q3KNV8-1
	PCGF3	ENST00000870362.1		c.525C>T	p.Arg175Arg	synonymous	Exon 10 of 12	ENSP00000540421.1

Frequencies

GnomAD3 genomes AF: 0.0511 AC: 7786 AN: 152220 Hom.: 286 Cov.: 33

Gnomad AFR AF: 0.0161

Gnomad AMI AF: 0.139

Gnomad AMR AF: 0.0613

Gnomad ASJ AF: 0.130

Gnomad EAS AF: 0.122

Gnomad SAS AF: 0.0576

Gnomad FIN AF: 0.0604

Gnomad MID AF: 0.0601

Gnomad NFE AF: 0.0572

Gnomad OTH AF: 0.0654

GnomAD2 exomes AF: 0.0643 AC: 15911 AN: 247314 AF XY: 0.0649

Gnomad AFR exome AF: 0.0150

Gnomad AMR exome AF: 0.0620

Gnomad ASJ exome AF: 0.136

Gnomad EAS exome AF: 0.118

Gnomad FIN exome AF: 0.0698

Gnomad NFE exome AF: 0.0562

Gnomad OTH exome AF: 0.0703

GnomAD4 exome AF: 0.0607 AC: 88554 AN: 1458356 Hom.: 3160 Cov.: 31 AF XY: 0.0609 AC XY: 44157 AN XY: 725046

African (AFR) AF: 0.0143 AC: 476 AN: 33390

American (AMR) AF: 0.0636 AC: 2819 AN: 44292

Ashkenazi Jewish (ASJ) AF: 0.134 AC: 3500 AN: 26070

East Asian (EAS) AF: 0.148 AC: 5863 AN: 39566

South Asian (SAS) AF: 0.0627 AC: 5376 AN: 85712

European-Finnish (FIN) AF: 0.0696 AC: 3710 AN: 53274

Middle Eastern (MID) AF: 0.0744 AC: 428 AN: 5752

European-Non Finnish (NFE) AF: 0.0564 AC: 62555 AN: 1110036

Other (OTH) AF: 0.0635 AC: 3827 AN: 60264

GnomAD4 genome AF: 0.0512 AC: 7793 AN: 152338 Hom.: 286 Cov.: 33 AF XY: 0.0515 AC XY: 3839 AN XY: 74480

African (AFR) AF: 0.0162 AC: 674 AN: 41588

American (AMR) AF: 0.0616 AC: 942 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.130 AC: 451 AN: 3468

East Asian (EAS) AF: 0.121 AC: 630 AN: 5188

South Asian (SAS) AF: 0.0578 AC: 279 AN: 4824

European-Finnish (FIN) AF: 0.0604 AC: 641 AN: 10616

Middle Eastern (MID) AF: 0.0680 AC: 20 AN: 294

European-Non Finnish (NFE) AF: 0.0572 AC: 3892 AN: 68028

Other (OTH) AF: 0.0647 AC: 137 AN: 2116

Alfa AF: 0.0578 Hom.: 217

Bravo AF: 0.0511

Asia WGS AF: 0.0670 AC: 232 AN: 3478

EpiCase AF: 0.0650

EpiControl AF: 0.0642

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.46
CADD	Benign	16
DANN	Benign	0.89
PhyloP100		1.0
Mutation Taster		=86/14	polymorphism (auto)

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs2242234;

hg19: chr4-755129;

COSMIC: COSV62858333;

COSMIC: COSV62858333;