rs2242234

Positions:

• chr4-761341-C-T

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_Moderate BP7 BA1

The NM_006315.7(PCGF3):​c.525C>T​(p.Arg175=) 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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PCGF3	NM_006315.7	c.525C>T	p.Arg175=	synonymous_variant	9/11	ENST00000362003.10
LOC124900163	XM_047416474.1	c.-1294G>A		5_prime_UTR_variant	2/2
PCGF3-AS1	NR_171661.1	n.3483G>A		non_coding_transcript_exon_variant	3/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PCGF3	ENST00000362003.10	c.525C>T	p.Arg175=	synonymous_variant	9/11	5	NM_006315.7	P1
PCGF3-AS1	ENST00000660016.1	n.1478G>A		non_coding_transcript_exon_variant	2/2

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

GnomAD3 exomes AF: 0.0643 AC: 15911 AN: 247314 Hom.: 681 AF XY: 0.0649 AC XY: 8717 AN XY: 134228

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 SAS exome AF: 0.0624

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

Gnomad4 AFR exome AF: 0.0143

Gnomad4 AMR exome AF: 0.0636

Gnomad4 ASJ exome AF: 0.134

Gnomad4 EAS exome AF: 0.148

Gnomad4 SAS exome AF: 0.0627

Gnomad4 FIN exome AF: 0.0696

Gnomad4 NFE exome AF: 0.0564

Gnomad4 OTH exome AF: 0.0635

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

Gnomad4 AFR AF: 0.0162

Gnomad4 AMR AF: 0.0616

Gnomad4 ASJ AF: 0.130

Gnomad4 EAS AF: 0.121

Gnomad4 SAS AF: 0.0578

Gnomad4 FIN AF: 0.0604

Gnomad4 NFE AF: 0.0572

Gnomad4 OTH AF: 0.0647

Alfa AF: 0.0579 Hom.: 172

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.46
CADD	Benign	16
DANN	Benign	0.89

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

Publications

LitVar

Other links and lift over

dbSNP: rs2242234; hg19: chr4-755129; COSMIC: COSV62858333; COSMIC: COSV62858333;