dbSNP rs78248125: PAGE4:p.Pro27Pro (chrX-49830999-C-G) – ACMG Classification: Likely_benign (-3 pts)

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2BP4_StrongBP7

The NM_007003.4(PAGE4):c.81C>G(p.Pro27Pro) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000017 in 1,178,463 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. In-silico tool predicts a benign outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. P27P) has been classified as Benign.

Frequency

Genomes: 𝑓 0.0000090 ( 0 hom., 0 hem., cov: 23)

Exomes 𝑓: 9.4e-7 ( 0 hom. 0 hem. )

Consequence

PAGE4
NM_007003.4 splice_region, synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.170

Publications

0 publications found

Variant links:

Genes affected

PAGE4 (HGNC:4108): (PAGE family member 4) This gene is a member of the GAGE family. The GAGE genes are expressed in a variety of tumors and in some fetal and reproductive tissues. This gene is strongly expressed in prostate and prostate cancer. It is also expressed in other male and female reproductive tissues including testis, fallopian tube, uterus, and placenta, as well as in testicular cancer and uterine cancer. The protein encoded by this gene shares sequence similarity with other GAGE/PAGE proteins, and also belongs to a family of CT (cancer-testis) antigens. The protein may play a role in benign and malignant prostate diseases. A related pseudogene is located on chromosome 7. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Jan 2016]

PAGE4 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.98).

BP7

Synonymous conserved (PhyloP=-0.17 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_007003.4. 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
	PAGE4	NM_007003.4	MANE Select	c.81C>G	p.Pro27Pro	splice_region synonymous	Exon 3 of 5	NP_008934.1	O60829
	PAGE4	NM_001318877.1		c.81C>G	p.Pro27Pro	splice_region synonymous	Exon 3 of 5	NP_001305806.1	O60829

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PAGE4	ENST00000218068.7	TSL:1 MANE Select	c.81C>G	p.Pro27Pro	splice_region synonymous	Exon 3 of 5	ENSP00000218068.6	O60829
PAGE4	ENST00000376141.5	TSL:5	c.81C>G	p.Pro27Pro	splice_region synonymous	Exon 3 of 5	ENSP00000365311.1	O60829
PAGE4	ENST00000715210.1		c.81C>G	p.Pro27Pro	splice_region synonymous	Exon 3 of 5	ENSP00000520416.1	O60829

Frequencies

GnomAD3 genomes

AF:

0.00000899

AC:

AN:

111276

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:

0.000168

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00000692

AC:

AN:

144594

AF XY:

0.00

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:

0.0000720

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

9.37e-7

AC:

AN:

1067187

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

340479

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

25786

American (AMR)

AF:

0.00

AC:

AN:

32226

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

18776

East Asian (EAS)

AF:

0.00

AC:

AN:

29600

South Asian (SAS)

AF:

0.00

AC:

AN:

50491

European-Finnish (FIN)

AF:

0.0000254

AC:

AN:

39332

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4088

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

821883

Other (OTH)

AF:

0.00

AC:

AN:

45005

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.00000899

AC:

AN:

111276

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

33494

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

30558

American (AMR)

AF:

0.00

AC:

AN:

10445

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2632

East Asian (EAS)

AF:

0.00

AC:

AN:

3588

South Asian (SAS)

AF:

0.00

AC:

AN:

2603

European-Finnish (FIN)

AF:

0.000168

AC:

AN:

5940

Middle Eastern (MID)

AF:

0.00

AC:

AN:

237

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

53093

Other (OTH)

AF:

0.00

AC:

AN:

1495

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.98

CADD

Benign

0.33

(source)

DANN

Benign

0.15

PhyloP100

-0.17

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over