X-55076103-C-A

Variant names:

• chrX-55076103-C-A
• rs868053071
• NM_001015038.3:c.62C>A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001015038.3(PAGE2B):​c.62C>A​(p.Ser21Tyr) 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. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 22)
• Consequence: PAGE2B NM_001015038.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.552

Genes affected

PAGE2B (HGNC:31805): (PAGE family member 2B)

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.08525121).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PAGE2B	NM_001015038.3	c.62C>A	p.Ser21Tyr	missense_variant	Exon 2 of 5	ENST00000374971.2	NP_001015038.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PAGE2B	ENST00000374971.2	c.62C>A	p.Ser21Tyr	missense_variant	Exon 2 of 5	1	NM_001015038.3	ENSP00000364110.1
PAGE2B	ENST00000374974.7	c.62C>A	p.Ser21Tyr	missense_variant	Exon 2 of 5	5		ENSP00000364113.3

Frequencies

GnomAD3 genomes Cov.: 22

GnomAD3 exomes AF: 0.00000548 AC: 1 AN: 182389 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 66987

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000724

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 22

Bravo AF: 0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jul 02, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.62C>A (p.S21Y) alteration is located in exon 2 (coding exon 1) of the PAGE2B gene. This alteration results from a C to A substitution at nucleotide position 62, causing the serine (S) at amino acid position 21 to be replaced by a tyrosine (Y). 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	0.11
BayesDel_addAF	Benign	-0.62	T
BayesDel_noAF	Benign	-0.94
CADD	Benign	3.5
DANN	Benign	0.95
DEOGEN2	Benign	0.016	.;T
FATHMM_MKL	Benign	0.0018	N
LIST_S2	Benign	0.79	T;T
M_CAP	Benign	0.00079	T
MetaRNN	Benign	0.085	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.0	.;M
PrimateAI	Uncertain	0.49	T
PROVEAN	Benign	-2.3	N;N
REVEL	Benign	0.038
Sift	Benign	1.0	T;T
Sift4G	Benign	0.27	T;T
Polyphen		1.0	.;D
Vest4		0.27
MutPred		0.29		Gain of solvent accessibility (P = 0.1683);Gain of solvent accessibility (P = 0.1683);
MVP		0.11
MPC		1.6
ClinPred		0.16	T
GERP RS		-0.73
Varity_R		0.080
gMVP		0.013

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

Other links and lift over

dbSNP: rs868053071; hg19: chrX-55102536;