chrX-55091400-C-T

Variant names:

• chrX-55091400-C-T
• NM_207339.4:c.262C>T

Variant summary

Our verdict is Likely benign. Variant got -1 ACMG points: 0P and 1B. BP4

The NM_207339.4(PAGE2):​c.262C>T​(p.Pro88Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 20)
  • Exomes 𝑓: 9.1e-7 (0 hom. 1 hem.)
  • Failed GnomAD Quality Control
• Consequence: PAGE2 NM_207339.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.157

Genes affected

PAGE2 (HGNC:31804): (PAGE family member 2)

ACMG classification

Verdict is Likely_benign. Variant got -1 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.38610145).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PAGE2	NM_207339.4	c.262C>T	p.Pro88Ser	missense_variant	Exon 4 of 5	ENST00000374968.9	NP_997222.1
PAGE2	XM_017029353.2	c.262C>T	p.Pro88Ser	missense_variant	Exon 4 of 5		XP_016884842.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PAGE2	ENST00000374968.9	c.262C>T	p.Pro88Ser	missense_variant	Exon 4 of 5	1	NM_207339.4	ENSP00000364107.4
PAGE2	ENST00000374965.5	c.211C>T	p.Pro71Ser	missense_variant	Exon 4 of 5	2		ENSP00000364104.1

Frequencies

GnomAD3 genomes Cov.: 20

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 9.12e-7 AC: 1 AN: 1095998 Hom.: 0 Cov.: 31 AF XY: 0.00000276 AC XY: 1 AN XY: 361708

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: 0.00000119

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 20

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jan 04, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.262C>T (p.P88S) alteration is located in exon 4 (coding exon 3) of the PAGE2 gene. This alteration results from a C to T substitution at nucleotide position 262, causing the proline (P) at amino acid position 88 to be replaced by a serine (S). 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	0.16
BayesDel_addAF	Benign	-0.38	T
BayesDel_noAF	Benign	-0.78
CADD	Benign	12
DANN	Uncertain	0.98
DEOGEN2	Benign	0.042	T;.
FATHMM_MKL	Benign	0.0017	N
LIST_S2	Benign	0.69	T;T
M_CAP	Benign	0.0018	T
MetaRNN	Benign	0.39	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.8	M;.
PROVEAN	Pathogenic	-5.9	D;D
REVEL	Benign	0.044
Sift	Benign	0.068	T;D
Sift4G	Benign	0.067	T;T
Polyphen		1.0	D;.
Vest4		0.26
MutPred		0.69		Gain of phosphorylation at P88 (P = 0.0203);.;
MVP		0.22
MPC		0.28
ClinPred		0.94	D
GERP RS		-1.1
Varity_R		0.13
gMVP		0.020

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

No publications associated with this variant yet.

Other links and lift over

hg19: chrX-55117833;