X-55221387-G-A

Variant names:

• chrX-55221387-G-A
• NM_001013435.3:c.5G>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001013435.3(PAGE5):​c.5G>A​(p.Ser2Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 23)
• Consequence: PAGE5 NM_001013435.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.116
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.15577668).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PAGE5	NM_001013435.3	c.5G>A	p.Ser2Asn	missense_variant	Exon 2 of 5	ENST00000374955.8	NP_001013453.1
PAGE5	NM_130467.5	c.65G>A	p.Ser22Asn	missense_variant	Exon 2 of 5		NP_569734.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PAGE5	ENST00000374955.8	c.5G>A	p.Ser2Asn	missense_variant	Exon 2 of 5	1	NM_001013435.3	ENSP00000364093.3
PAGE5	ENST00000289619.9	c.65G>A	p.Ser22Asn	missense_variant	Exon 2 of 5	1		ENSP00000289619.5
PAGE5	ENST00000374952.1	c.5G>A	p.Ser2Asn	missense_variant	Exon 2 of 5	5		ENSP00000364090.1

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 23

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Mar 07, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.65G>A (p.S22N) alteration is located in exon 2 (coding exon 2) of the PAGE5 gene. This alteration results from a G to A substitution at nucleotide position 65, causing the serine (S) at amino acid position 22 to be replaced by an asparagine (N). 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	0.33
BayesDel_addAF	Benign	-0.37	T
BayesDel_noAF	Benign	-0.77
CADD	Benign	16
DANN	Benign	0.97
DEOGEN2	Benign	0.018	T;.;.
FATHMM_MKL	Benign	0.0075	N
LIST_S2	Benign	0.72	T;T;T
M_CAP	Benign	0.0051	T
MetaRNN	Benign	0.16	T;T;T
MetaSVM	Benign	-0.88	T
MutationAssessor	Uncertain	2.5	M;.;.
PhyloP100		0.12
PrimateAI	Uncertain	0.49	T
PROVEAN	Benign	-1.6	N;N;N
REVEL	Benign	0.062
Sift	Pathogenic	0.0	D;D;D
Sift4G	Pathogenic	0.0	D;D;D
Polyphen		1.0	D;.;.
Vest4		0.18
MutPred		0.12		Loss of phosphorylation at S22 (P = 0.0061);.;.;
MVP		0.29
MPC		0.66
ClinPred		0.92	D
GERP RS		0.15
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.44
gMVP		0.019
Mutation Taster		=98/2	polymorphism

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

Other links and lift over

hg19: chrX-55247820;