Variant chrX-55221788-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001013435.3(PAGE5):c.103A>G(p.Lys35Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000497 in 1,208,128 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 1 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000018 ( 0 hom., 0 hem., cov: 22)

Exomes 𝑓: 0.0000036 ( 0 hom. 1 hem. )

Consequence

PAGE5
NM_001013435.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.640

Variant links:

Genes affected

PAGE5 (HGNC:29992): (PAGE family member 5) This gene is a member of family of proteins that are expressed in a variety of tumors and in some fetal and reproductive tissues. The encoded protein may protect cells from programmed cell death. Multiple alternatively spliced transcript variants encoding distinct isoforms have been found. [provided by RefSeq, Jan 2015]

PAGE5 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.09365156).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PAGE5	NM_001013435.3 linkuse as main transcript	c.103A>G	p.Lys35Glu	missense_variant	3/5	ENST00000374955.8
PAGE5	NM_130467.5 linkuse as main transcript	c.163A>G	p.Lys55Glu	missense_variant	3/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PAGE5	ENST00000374955.8 linkuse as main transcript	c.103A>G	p.Lys35Glu	missense_variant	3/5	1	NM_001013435.3	P2	Q96GU1-2
PAGE5	ENST00000289619.9 linkuse as main transcript	c.163A>G	p.Lys55Glu	missense_variant	3/5	1		A2	Q96GU1-1
PAGE5	ENST00000374952.1 linkuse as main transcript	c.103A>G	p.Lys35Glu	missense_variant	3/5	5

Frequencies

GnomAD3 genomes

AF:

0.0000179

AC:

AN:

111434

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

33614

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:

0.0000376

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000559

AC:

AN:

178953

Hom.:

AF XY:

0.00

AC XY:

AN XY:

63779

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 SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000126

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000365

AC:

AN:

1096694

Hom.:

Cov.:

AF XY:

0.00000276

AC XY:

AN XY:

362282

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000475

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000179

AC:

AN:

111434

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

33614

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000376

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000189

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 27, 2023

The c.163A>G (p.K55E) alteration is located in exon 3 (coding exon 3) of the PAGE5 gene. This alteration results from a A to G substitution at nucleotide position 163, causing the lysine (K) at amino acid position 55 to be replaced by a glutamic acid (E). 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

0.091

BayesDel_addAF

Benign

-0.45

BayesDel_noAF

Benign

-0.89

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.0015

T;.;.

FATHMM_MKL

Benign

0.0019

LIST_S2

Benign

0.70

T;T;T

M_CAP

Benign

0.0019

MetaRNN

Benign

0.094

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.1

L;.;.

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Uncertain

0.48

PROVEAN

Benign

-0.17

N;N;N

REVEL

Benign

0.073

Sift

Benign

0.25

T;T;D

Sift4G

Benign

0.55

T;T;T

Polyphen

0.83

P;.;.

Vest4

0.11

MutPred

0.39

Loss of methylation at K55 (P = 3e-04);.;.;

MVP

0.26

MPC

0.40

ClinPred

0.14

GERP RS

-0.35

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.14

gMVP

0.0074

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.090

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