Genetic Variant NM_032673.3:c.719G>A (chr2-74505352-C-T) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_032673.3(PCGF1):c.719G>A(p.Arg240His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000254 in 1,608,154 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00011 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00027 ( 0 hom. )

Consequence

PCGF1
NM_032673.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.03

Publications

2 publications found

Variant links:

Genes affected

PCGF1 (HGNC:17615): (polycomb group ring finger 1) PCGF1 is a mammalian homolog of the Drosophila polycomb group genes, which act as transcriptional repressors to regulate anterior-posterior patterning in early embryonic development (Nunes et al., 2001 [PubMed 11287196]). See also PCGF2 (MIM 600346).[supplied by OMIM, Aug 2008]

PCGF1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.1258679).

BS2

High AC in GnomAd4 at 17 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032673.3. 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
	PCGF1	NM_032673.3	MANE Select	c.719G>A	p.Arg240His	missense	Exon 8 of 9	NP_116062.2	Q9BSM1-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PCGF1	ENST00000233630.11	TSL:1 MANE Select	c.719G>A	p.Arg240His	missense	Exon 8 of 9	ENSP00000233630.6	Q9BSM1-1
PCGF1	ENST00000475863.5	TSL:1	n.895G>A		non_coding_transcript_exon	Exon 7 of 8
PCGF1	ENST00000489914.1	TSL:1	n.127G>A		non_coding_transcript_exon	Exon 2 of 2

Frequencies

GnomAD3 genomes

AF:

0.000112

AC:

AN:

152068

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000221

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000104

AC:

AN:

240758

AF XY:

0.000108

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000212

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000269

AC:

392

AN:

1456086

Hom.:

Cov.:

AF XY:

0.000294

AC XY:

213

AN XY:

723748

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33392

American (AMR)

AF:

0.00

AC:

AN:

43852

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26020

East Asian (EAS)

AF:

0.0000253

AC:

AN:

39572

South Asian (SAS)

AF:

0.000106

AC:

AN:

85202

European-Finnish (FIN)

AF:

0.0000754

AC:

AN:

53046

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5746

European-Non Finnish (NFE)

AF:

0.000337

AC:

374

AN:

1109084

Other (OTH)

AF:

0.0000665

AC:

AN:

60172

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.476

Heterozygous variant carriers

109

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

100

<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:

0.000112

AC:

AN:

152068

Hom.:

Cov.:

AF XY:

0.000108

AC XY:

AN XY:

74270

show subpopulations

African (AFR)

AF:

0.0000483

AC:

AN:

41376

American (AMR)

AF:

0.00

AC:

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5194

South Asian (SAS)

AF:

0.00

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10596

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.000221

AC:

AN:

68012

Other (OTH)

AF:

0.00

AC:

AN:

2086

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.000144

Hom.:

Bravo

AF:

0.000102

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.0000906

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.097

BayesDel_addAF

Benign

-0.40

BayesDel_noAF

Benign

-0.53

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.052

Eigen

Benign

-0.37

Eigen_PC

Benign

-0.17

FATHMM_MKL

Benign

0.74

LIST_S2

Uncertain

0.90

M_CAP

Benign

0.0060

MetaRNN

Benign

0.13

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.18

PhyloP100

2.0

PrimateAI

Benign

0.32

PROVEAN

Benign

-0.48

REVEL

Benign

0.060

Sift

Benign

0.25

Sift4G

Benign

0.34

Polyphen

0.0010

Vest4

0.23

MVP

0.27

MPC

1.0

ClinPred

0.050

GERP RS

3.8

Varity_R

0.19

gMVP

0.57

Mutation Taster

=64/36

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over