Genetic Variant PAGE1:p.Gly56Gly (chrX-49691373-C-T) – ACMG Classification: Benign (-17 pts)

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2

The NM_003785.4(PAGE1):c.168G>A(p.Gly56Gly) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00539 in 1,189,221 control chromosomes in the GnomAD database, including 16 homozygotes. There are 2,070 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0037 ( 1 hom., 114 hem., cov: 23)

Exomes 𝑓: 0.0056 ( 15 hom. 1956 hem. )

Consequence

PAGE1
NM_003785.4 splice_region, synonymous

Scores

Splicing: ADA: 0.00001910

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -1.86

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -17 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.87).

BP6

Variant X-49691373-C-T is Benign according to our data. Variant chrX-49691373-C-T is described in ClinVar as [Benign]. Clinvar id is 789252.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chrX-49691373-C-T is described in Lovd as [Likely_benign].

BP7

Synonymous conserved (PhyloP=-1.86 with no splicing effect.

BS2

High Hemizygotes in GnomAd4 at 114 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PAGE1	NM_003785.4 link	c.168G>A	p.Gly56Gly	splice_region_variant, synonymous_variant	Exon 4 of 6	ENST00000376150.4	NP_003776.2	O75459
PAGE1	XM_011543998.3 link	c.168G>A	p.Gly56Gly	splice_region_variant, synonymous_variant	Exon 4 of 6		XP_011542300.1	O75459

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PAGE1	ENST00000376150.4 link	c.168G>A	p.Gly56Gly	splice_region_variant, synonymous_variant	Exon 4 of 6	1	NM_003785.4	ENSP00000365320.3		O75459

Frequencies

GnomAD3 genomes

AF:

0.00371

AC:

413

AN:

111449

Hom.:

Cov.:

AF XY:

0.00339

AC XY:

114

AN XY:

33669

show subpopulations

Gnomad AFR

AF:

0.000684

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00420

Gnomad ASJ

AF:

0.000378

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00191

Gnomad FIN

AF:

0.000503

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00637

Gnomad OTH

AF:

0.000670

GnomAD3 exomes

AF:

0.00348

AC:

589

AN:

169157

Hom.:

AF XY:

0.00373

AC XY:

212

AN XY:

56857

show subpopulations

Gnomad AFR exome

AF:

0.000938

Gnomad AMR exome

AF:

0.00187

Gnomad ASJ exome

AF:

0.000602

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00288

Gnomad FIN exome

AF:

0.000447

Gnomad NFE exome

AF:

0.00597

Gnomad OTH exome

AF:

0.00293

GnomAD4 exome

AF:

0.00557

AC:

6000

AN:

1077721

Hom.:

Cov.:

AF XY:

0.00565

AC XY:

1956

AN XY:

346501

show subpopulations

Gnomad4 AFR exome

AF:

0.000937

Gnomad4 AMR exome

AF:

0.00188

Gnomad4 ASJ exome

AF:

0.000430

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00270

Gnomad4 FIN exome

AF:

0.000945

Gnomad4 NFE exome

AF:

0.00666

Gnomad4 OTH exome

AF:

0.00420

GnomAD4 genome

AF:

0.00370

AC:

413

AN:

111500

Hom.:

Cov.:

AF XY:

0.00338

AC XY:

114

AN XY:

33730

show subpopulations

Gnomad4 AFR

AF:

0.000683

Gnomad4 AMR

AF:

0.00420

Gnomad4 ASJ

AF:

0.000378

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00192

Gnomad4 FIN

AF:

0.000503

Gnomad4 NFE

AF:

0.00637

Gnomad4 OTH

AF:

0.000661

Alfa

AF:

0.00515

Hom.:

212

Bravo

AF:

0.00346

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Aug 09, 2017

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

0.35

DANN

Benign

0.30

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000019

dbscSNV1_RF

Benign

0.0

SpliceAI score (max)

0.050

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