Genetic Variant PCGF3:c.600+6A>G (chr4-761422-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Variant links:

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]

PCGF3 links:

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

PCGF3-AS1 links:

LOC124900163 (HGNC:):

LOC124900163 links:

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ACMG classification

Classification was made for transcript

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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PCGF3	NM_006315.7 link	c.600+6A>G		splice_region_variant, intron_variant	Intron 9 of 10	ENST00000362003.10	NP_006306.2	Q3KNV8-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PCGF3	ENST00000362003.10 link	c.600+6A>G		splice_region_variant, intron_variant	Intron 9 of 10	5	NM_006315.7	ENSP00000354724.5		Q3KNV8-1

Frequencies

GnomAD3 genomes

AF:

0.0759

AC:

11551

AN:

152232

Hom.:

504

Cov.:

show subpopulations

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

show subpopulations

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.:

AF XY:

0.0843

AC XY:

60477

AN XY:

717006

show subpopulations

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

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.487

Heterozygous variant carriers

5027

10053

15080

20106

25133

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

3022

6044

9066

12088

15110

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0759

AC:

11558

AN:

152350

Hom.:

504

Cov.:

AF XY:

0.0794

AC XY:

5918

AN XY:

74494

show subpopulations

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:

AN:

294

European-Non Finnish (NFE)

AF:

0.0834

AC:

5673

AN:

68032

Other (OTH)

AF:

0.0747

AC:

158

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

572

1145

1717

2290

2862

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

140

280

420

560

700

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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 v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

0.52

(source)

DANN

Benign

0.67

PhyloP100

-0.024

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over