rs200598284

Variant names:

• chrX-55076611-C-T
• rs200598284
• NM_001015038.3:c.127C>T

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Moderate BS2

The NM_001015038.3(PAGE2B):​c.127C>T​(p.Pro43Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000373 in 1,205,516 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 10 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000091 (0 hom., 0 hem., cov: 21)
  • Exomes 𝑓: 0.000032 (0 hom. 10 hem.)
• Consequence: PAGE2B NM_001015038.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.765
• Publications: 0 publications found

Genes affected

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

ACMG classification

Our verdict: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.10340229).
• BS2: High Hemizygotes in GnomAdExome4 at 10 gene

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.127C>T	p.Pro43Ser	missense	Exon 3 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.127C>T	p.Pro43Ser	missense	Exon 3 of 5	ENSP00000364110.1	Q5JRK9
	PAGE2B	ENST00000879400.1		c.127C>T	p.Pro43Ser	missense	Exon 2 of 4	ENSP00000549459.1
	PAGE2B	ENST00000374974.7	TSL:5	c.127C>T	p.Pro43Ser	missense	Exon 3 of 5	ENSP00000364113.3	Q5JRL0

Frequencies

GnomAD3 genomes AF: 0.0000910 AC: 10 AN: 109920 Hom.: 0 Cov.: 21

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000491

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000856

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000189

Gnomad OTH AF: 0.000678

GnomAD2 exomes AF: 0.0000170 AC: 3 AN: 176930 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000372

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000733

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.000227

GnomAD4 exome AF: 0.0000319 AC: 35 AN: 1095550 Hom.: 0 Cov.: 30 AF XY: 0.0000277 AC XY: 10 AN XY: 361244

African (AFR) AF: 0.00 AC: 0 AN: 26347

American (AMR) AF: 0.00 AC: 0 AN: 34948

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19336

East Asian (EAS) AF: 0.000199 AC: 6 AN: 30181

South Asian (SAS) AF: 0.00 AC: 0 AN: 53310

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40396

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4131

European-Non Finnish (NFE) AF: 0.00000119 AC: 1 AN: 840888

Other (OTH) AF: 0.000609 AC: 28 AN: 46013

GnomAD4 genome AF: 0.0000909 AC: 10 AN: 109966 Hom.: 0 Cov.: 21 AF XY: 0.00 AC XY: 0 AN XY: 32222

African (AFR) AF: 0.00 AC: 0 AN: 30180

American (AMR) AF: 0.000491 AC: 5 AN: 10188

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2638

East Asian (EAS) AF: 0.000859 AC: 3 AN: 3491

South Asian (SAS) AF: 0.00 AC: 0 AN: 2533

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 5708

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 212

European-Non Finnish (NFE) AF: 0.0000189 AC: 1 AN: 52845

Other (OTH) AF: 0.000670 AC: 1 AN: 1493

Alfa AF: 0.000142 Hom.: 1

Bravo AF: 0.0000680

ExAC AF: 0.0000330 AC: 4

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.54	T
BayesDel_noAF	Benign	-0.82
CADD	Benign	14
DANN	Uncertain	0.98
DEOGEN2	Benign	0.028	T
FATHMM_MKL	Benign	0.0015	N
LIST_S2	Benign	0.80	T
M_CAP	Benign	0.00080	T
MetaRNN	Benign	0.10	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.1	M
PhyloP100		-0.77
PrimateAI	Benign	0.43	T
PROVEAN	Pathogenic	-6.1	D
REVEL	Benign	0.044
Sift	Uncertain	0.0090	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.24
MVP		0.014
MPC		1.4
ClinPred		0.81	D
GERP RS		-1.9
Varity_R		0.29
gMVP		0.025
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: rs200598284; hg19: chrX-55103044;