Genetic Variant NM_006315.7: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:

Genome browser will be placed here

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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