Variant X-55260590-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_001017931.3(PAGE3):c.263C>T(p.Pro88Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000273 in 564,435 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 66 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 12/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00018 ( 0 hom., 5 hem., cov: 22)

Exomes 𝑓: 0.00030 ( 0 hom. 61 hem. )

Consequence

PAGE3
NM_001017931.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.327

Variant links:

Genes affected

PAGE3 (HGNC:4110): (PAGE family member 3) This gene is a member of family of proteins that are expressed in a variety of tumors and in some fetal and reproductive tissues. Multiple alternatively spliced transcript variants have been observed. [provided by RefSeq, Jan 2015]

PAGE3 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.011217713).

BP6

Variant X-55260590-G-A is Benign according to our data. Variant chrX-55260590-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2660694.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Hemizygotes in GnomAd4 at 5 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PAGE3	NM_001017931.3 linkuse as main transcript	c.263C>T	p.Pro88Leu	missense_variant	4/5	ENST00000374951.6	NP_001017931.3	Q5JUK9
PAGE3	NM_001171252.2 linkuse as main transcript	c.263C>T	p.Pro88Leu	missense_variant	4/5		NP_001164723.2	Q5JUK9
PAGE3	NM_001303613.2 linkuse as main transcript	c.263C>T	p.Pro88Leu	missense_variant	4/5		NP_001290542.2	Q5JUK9
PAGE3	XM_017029282.3 linkuse as main transcript	c.263C>T	p.Pro88Leu	missense_variant	4/5		XP_016884771.1	Q5JUK9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PAGE3	ENST00000374951.6 linkuse as main transcript	c.263C>T	p.Pro88Leu	missense_variant	4/5	1	NM_001017931.3	ENSP00000364089.1		Q5JUK9
PAGE3	ENST00000519203.1 linkuse as main transcript	c.263C>T	p.Pro88Leu	missense_variant	4/5	1		ENSP00000429571.1		Q5JUK9

Frequencies

GnomAD3 genomes

AF:

0.000189

AC:

AN:

111047

Hom.:

Cov.:

AF XY:

0.000180

AC XY:

AN XY:

33321

show subpopulations

Gnomad AFR

AF:

0.0000655

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000966

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00367

Gnomad SAS

AF:

0.00113

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000189

Gnomad OTH

AF:

0.000674

GnomAD3 exomes

AF:

0.000332

AC:

AN:

180893

Hom.:

AF XY:

0.000366

AC XY:

AN XY:

65517

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00331

Gnomad SAS exome

AF:

0.000643

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000248

Gnomad OTH exome

AF:

0.000225

GnomAD4 exome

AF:

0.000296

AC:

134

AN:

453342

Hom.:

Cov.:

AF XY:

0.000363

AC XY:

AN XY:

167898

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00219

Gnomad4 SAS exome

AF:

0.00111

Gnomad4 FIN exome

AF:

0.0000250

Gnomad4 NFE exome

AF:

0.0000748

Gnomad4 OTH exome

AF:

0.000365

GnomAD4 genome

AF:

0.000180

AC:

AN:

111093

Hom.:

Cov.:

AF XY:

0.000150

AC XY:

AN XY:

33377

show subpopulations

Gnomad4 AFR

AF:

0.0000653

Gnomad4 AMR

AF:

0.0000965

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00340

Gnomad4 SAS

AF:

0.00114

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000189

Gnomad4 OTH

AF:

0.000666

Bravo

AF:

0.000340

ExAC

AF:

0.000313

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Feb 01, 2023

PAGE3: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.18

BayesDel_addAF

Benign

-0.85

BayesDel_noAF

Benign

-0.99

CADD

Benign

6.6

DANN

Benign

0.41

DEOGEN2

Benign

0.053

T;T

FATHMM_MKL

Benign

0.0048

LIST_S2

Benign

0.68

.;T

M_CAP

Benign

0.0012

MetaRNN

Benign

0.011

T;T

MetaSVM

Benign

-0.98

PrimateAI

Benign

0.32

PROVEAN

Pathogenic

-8.9

D;D

REVEL

Benign

0.070

Sift

Uncertain

0.025

D;D

Sift4G

Uncertain

0.058

T;T

Polyphen

0.089

B;B

Vest4

0.049

MVP

0.040

MPC

0.0052

ClinPred

0.042

GERP RS

0.087

Varity_R

0.17

gMVP

0.031

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

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