chrX-55076108-C-T

Variant names:

• chrX-55076108-C-T
• rs752541823
• NM_001015038.3:c.67C>T

Variant summary

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

The NM_001015038.3(PAGE2B):​c.67C>T​(p.Pro23Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000101 in 1,093,522 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. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P23A) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 22)
  • Exomes 𝑓: 0.000010 (0 hom. 0 hem.)
• Consequence: PAGE2B NM_001015038.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.36
• Publications: 0 publications found

Genes affected

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

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=0.12849858).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001015038.3. 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
	PAGE2B	NM_001015038.3	MANE Select	c.67C>T	p.Pro23Ser	missense	Exon 2 of 5	NP_001015038.1	Q5JRK9

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PAGE2B	ENST00000374971.2	TSL:1 MANE Select	c.67C>T	p.Pro23Ser	missense	Exon 2 of 5	ENSP00000364110.1	Q5JRK9
	PAGE2B	ENST00000879400.1		c.67C>T	p.Pro23Ser	missense	Exon 1 of 4	ENSP00000549459.1
	PAGE2B	ENST00000374974.7	TSL:5	c.67C>T	p.Pro23Ser	missense	Exon 2 of 5	ENSP00000364113.3	Q5JRL0

Frequencies

GnomAD3 genomes Cov.: 22

GnomAD4 exome AF: 0.0000101 AC: 11 AN: 1093522 Hom.: 0 Cov.: 29 AF XY: 0.00 AC XY: 0 AN XY: 359416

African (AFR) AF: 0.00 AC: 0 AN: 26259

American (AMR) AF: 0.00 AC: 0 AN: 35076

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19337

East Asian (EAS) AF: 0.00 AC: 0 AN: 30156

South Asian (SAS) AF: 0.00 AC: 0 AN: 53742

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40501

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4115

European-Non Finnish (NFE) AF: 0.0000131 AC: 11 AN: 838390

Other (OTH) AF: 0.00 AC: 0 AN: 45946

GnomAD4 genome Cov.: 22

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.095
BayesDel_addAF	Benign	-0.57	T
BayesDel_noAF	Benign	-1.1
CADD	Benign	0.86
DANN	Benign	0.97
DEOGEN2	Benign	0.016	T
FATHMM_MKL	Benign	0.00072	N
LIST_S2	Benign	0.61	T
M_CAP	Benign	0.0011	T
MetaRNN	Benign	0.13	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.1	M
PhyloP100		-2.4
PrimateAI	Benign	0.40	T
PROVEAN	Uncertain	-2.7	D
REVEL	Benign	0.038
Sift	Uncertain	0.021	D
Sift4G	Benign	0.55	T
Polyphen		0.90	P
Vest4		0.059
MutPred		0.52		Gain of phosphorylation at P23 (P = 0.0184)
MVP		0.014
MPC		1.2
ClinPred		0.62	D
GERP RS		-1.2
Varity_R		0.056
gMVP		0.016
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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

dbSNP: rs752541823; hg19: chrX-55102541;