Genetic Variant PAGE1:p.Arg12Lys (chrX-49694736-C-T) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_003785.4(PAGE1):c.35G>A(p.Arg12Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000192 in 1,197,836 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 63 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000062 ( 0 hom., 1 hem., cov: 23)

Exomes 𝑓: 0.00021 ( 0 hom. 62 hem. )

Consequence

PAGE1
NM_003785.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.908

Publications

1 publications found

Variant links:

Genes affected

PAGE1 (HGNC:4107): (PAGE family member 1) This gene belongs to a family of genes that are expressed in a variety of tumors but not in normal tissues, except for the testis. Unlike the other gene family members, this gene does not encode an antigenic peptide. Nothing is presently known about the function of this protein. [provided by RefSeq, Jul 2008]

PAGE1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.062268823).

BS2

High Hemizygotes in GnomAdExome4 at 62 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003785.4. 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
	PAGE1	NM_003785.4	MANE Select	c.35G>A	p.Arg12Lys	missense	Exon 2 of 6	NP_003776.2	O75459

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PAGE1	ENST00000376150.4	TSL:1 MANE Select	c.35G>A	p.Arg12Lys	missense	Exon 2 of 6	ENSP00000365320.3	O75459

Frequencies

GnomAD3 genomes

AF:

0.0000624

AC:

AN:

112248

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

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:

0.000131

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000897

AC:

AN:

178349

AF XY:

0.0000635

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:

0.0000628

Gnomad NFE exome

AF:

0.000161

Gnomad OTH exome

AF:

0.000453

GnomAD4 exome

AF:

0.000205

AC:

223

AN:

1085588

Hom.:

Cov.:

AF XY:

0.000176

AC XY:

AN XY:

351838

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

26181

American (AMR)

AF:

0.00

AC:

AN:

34867

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19255

East Asian (EAS)

AF:

0.00

AC:

AN:

30133

South Asian (SAS)

AF:

0.00

AC:

AN:

52701

European-Finnish (FIN)

AF:

0.0000741

AC:

AN:

40489

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4107

European-Non Finnish (NFE)

AF:

0.000242

AC:

201

AN:

832158

Other (OTH)

AF:

0.000416

AC:

AN:

45697

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.446

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

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

GnomAD4 genome

AF:

0.0000624

AC:

AN:

112248

Hom.:

Cov.:

AF XY:

0.0000291

AC XY:

AN XY:

34414

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

30910

American (AMR)

AF:

0.00

AC:

AN:

10568

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2647

East Asian (EAS)

AF:

0.00

AC:

AN:

3607

South Asian (SAS)

AF:

0.00

AC:

AN:

2691

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6083

Middle Eastern (MID)

AF:

0.00

AC:

AN:

238

European-Non Finnish (NFE)

AF:

0.000131

AC:

AN:

53301

Other (OTH)

AF:

0.00

AC:

AN:

1516

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.600

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:

0.0000712

Hom.:

Bravo

AF:

0.0000793

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00

AC:

ExAC

AF:

0.0000412

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

0.16

BayesDel_addAF

Benign

-0.69

BayesDel_noAF

Benign

-0.98

CADD

Benign

0.38

(source)

DANN

Benign

0.60

DEOGEN2

Benign

0.012

FATHMM_MKL

Benign

0.0021

LIST_S2

Benign

0.36

M_CAP

Benign

0.0011

MetaRNN

Benign

0.062

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.7

PhyloP100

-0.91

PrimateAI

Benign

0.35

PROVEAN

Benign

-1.4

REVEL

Benign

0.032

Sift

Uncertain

0.025

Sift4G

Benign

0.10

Polyphen

0.048

Vest4

0.082

MVP

0.030

MPC

0.22

ClinPred

0.016

GERP RS

-1.3

Varity_R

0.15

gMVP

0.050

Mutation Taster

=100/0

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

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over