Genetic Variant PAGE2B:p.Pro43Ser (chrX-55076611-C-T) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_001015038.3(PAGE2B):c.127C>T(p.Pro43Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000373 in 1,205,516 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 10 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000091 ( 0 hom., 0 hem., cov: 21)

Exomes 𝑓: 0.000032 ( 0 hom. 10 hem. )

Consequence

PAGE2B
NM_001015038.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.765

Variant links:

Genes affected

PAGE2B (HGNC:31805): (PAGE family member 2B)

PAGE2B links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.10340229).

BS2

High Hemizygotes in GnomAdExome4 at 10 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PAGE2B	NM_001015038.3 link	c.127C>T	p.Pro43Ser	missense_variant	Exon 3 of 5	ENST00000374971.2	NP_001015038.1	Q5JRK9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PAGE2B	ENST00000374971.2 link	c.127C>T	p.Pro43Ser	missense_variant	Exon 3 of 5	1	NM_001015038.3	ENSP00000364110.1		Q5JRK9
PAGE2B	ENST00000374974.7 link	c.127C>T	p.Pro43Ser	missense_variant	Exon 3 of 5	5		ENSP00000364113.3		Q5JRL0

Frequencies

GnomAD3 genomes

AF:

0.0000910

AC:

AN:

109920

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

32166

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000491

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000856

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000189

Gnomad OTH

AF:

0.000678

GnomAD3 exomes

AF:

0.0000170

AC:

AN:

176930

Hom.:

AF XY:

0.00

AC XY:

AN XY:

61976

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000372

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000733

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000227

GnomAD4 exome

AF:

0.0000319

AC:

AN:

1095550

Hom.:

Cov.:

AF XY:

0.0000277

AC XY:

AN XY:

361244

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000199

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000119

Gnomad4 OTH exome

AF:

0.000609

GnomAD4 genome

AF:

0.0000909

AC:

AN:

109966

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

32222

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000491

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000859

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000189

Gnomad4 OTH

AF:

0.000670

Alfa

AF:

0.000142

Hom.:

Bravo

AF:

0.0000680

ExAC

AF:

0.0000330

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Mar 18, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.127C>T (p.P43S) alteration is located in exon 3 (coding exon 2) of the PAGE2B gene. This alteration results from a C to T substitution at nucleotide position 127, causing the proline (P) at amino acid position 43 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.54

BayesDel_noAF

Benign

-0.82

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.028

.;T

FATHMM_MKL

Benign

0.0015

LIST_S2

Benign

0.80

T;T

M_CAP

Benign

0.00080

MetaRNN

Benign

0.10

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.1

.;M

PrimateAI

Benign

0.43

PROVEAN

Pathogenic

-6.1

D;D

REVEL

Benign

0.044

Sift

Uncertain

0.0090

D;D

Sift4G

Pathogenic

0.0

D;D

Polyphen

1.0

.;D

Vest4

0.24

MVP

0.014

MPC

1.4

ClinPred

0.81

GERP RS

-1.9

Varity_R

0.29

gMVP

0.025

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over