rs2242235

Variant names:

• chr4-761422-A-G
• rs2242235
• NM_006315.7:c.600+6A>G

Your query was ambiguous. Multiple possible variants found:

• chr4-761422-A-G
• chr4-761422-A-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006315.7(PCGF3):​c.600+6A>G variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0811 in 1,596,662 control chromosomes in the GnomAD database, including 5,911 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.076 (504 hom., cov: 33)
  • Exomes 𝑓: 0.082 (5407 hom.)
• Consequence: PCGF3 NM_006315.7 splice_region, intron
• Scores: Splicing: ADA: 0.00006706
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0240
• Publications: 13 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.135 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.600+6A>G		splice_region intron	N/A	NP_006306.2
	PCGF3	NM_001317836.3		c.600+6A>G		splice_region intron	N/A	NP_001304765.1	Q3KNV8-1
	PCGF3	NM_001395245.1		c.600+6A>G		splice_region intron	N/A	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.600+6A>G		splice_region intron	N/A	ENSP00000354724.5	Q3KNV8-1
	PCGF3	ENST00000470161.6	TSL:1	c.600+6A>G		splice_region intron	N/A	ENSP00000420489.2	Q3KNV8-1
	PCGF3	ENST00000870362.1		c.600+6A>G		splice_region intron	N/A	ENSP00000540421.1

Frequencies

GnomAD3 genomes AF: 0.0759 AC: 11551 AN: 152232 Hom.: 504 Cov.: 33

Gnomad AFR AF: 0.0432

Gnomad AMI AF: 0.0186

Gnomad AMR AF: 0.0825

Gnomad ASJ AF: 0.0968

Gnomad EAS AF: 0.0710

Gnomad SAS AF: 0.145

Gnomad FIN AF: 0.115

Gnomad MID AF: 0.117

Gnomad NFE AF: 0.0834

Gnomad OTH AF: 0.0712

GnomAD2 exomes AF: 0.0913 AC: 21577 AN: 236314 AF XY: 0.0942

Gnomad AFR exome AF: 0.0409

Gnomad AMR exome AF: 0.0976

Gnomad ASJ exome AF: 0.0938

Gnomad EAS exome AF: 0.0730

Gnomad FIN exome AF: 0.109

Gnomad NFE exome AF: 0.0813

Gnomad OTH exome AF: 0.0894

GnomAD4 exome AF: 0.0816 AC: 117908 AN: 1444312 Hom.: 5407 Cov.: 31 AF XY: 0.0843 AC XY: 60477 AN XY: 717006

African (AFR) AF: 0.0421 AC: 1379 AN: 32780

American (AMR) AF: 0.0946 AC: 4011 AN: 42386

Ashkenazi Jewish (ASJ) AF: 0.0956 AC: 2456 AN: 25692

East Asian (EAS) AF: 0.0890 AC: 3454 AN: 38788

South Asian (SAS) AF: 0.144 AC: 12069 AN: 83962

European-Finnish (FIN) AF: 0.107 AC: 5671 AN: 53150

Middle Eastern (MID) AF: 0.0951 AC: 542 AN: 5702

European-Non Finnish (NFE) AF: 0.0755 AC: 83221 AN: 1102116

Other (OTH) AF: 0.0855 AC: 5105 AN: 59736

GnomAD4 genome AF: 0.0759 AC: 11558 AN: 152350 Hom.: 504 Cov.: 33 AF XY: 0.0794 AC XY: 5918 AN XY: 74494

African (AFR) AF: 0.0432 AC: 1798 AN: 41596

American (AMR) AF: 0.0824 AC: 1261 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.0968 AC: 336 AN: 3472

East Asian (EAS) AF: 0.0712 AC: 369 AN: 5186

South Asian (SAS) AF: 0.144 AC: 693 AN: 4828

European-Finnish (FIN) AF: 0.115 AC: 1218 AN: 10612

Middle Eastern (MID) AF: 0.119 AC: 35 AN: 294

European-Non Finnish (NFE) AF: 0.0834 AC: 5673 AN: 68032

Other (OTH) AF: 0.0747 AC: 158 AN: 2116

Alfa AF: 0.0795 Hom.: 1176

Bravo AF: 0.0693

Asia WGS AF: 0.145 AC: 505 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.52
DANN	Benign	0.67
PhyloP100		-0.024
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000067
dbscSNV1_RF	Benign	0.0020
SpliceAI score (max)		0.070		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: rs2242235;

hg19: chr4-755210;

COSMIC: COSV62860610;

COSMIC: COSV62860610;