chrX-55077503-C-A

Variant names:

• chrX-55077503-C-A
• rs781620826
• NM_001015038.3:c.298C>A

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.298C>A​(p.Leu100Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000638 in 1,097,838 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. 15/21 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)
  • Exomes 𝑓: 0.0000064 (0 hom. 0 hem.)
• Consequence: PAGE2B NM_001015038.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.239
• 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=0.07862738).

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.298C>A	p.Leu100Ile	missense	Exon 4 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.298C>A	p.Leu100Ile	missense	Exon 4 of 5	ENSP00000364110.1	Q5JRK9
	PAGE2B	ENST00000879400.1		c.298C>A	p.Leu100Ile	missense	Exon 3 of 4	ENSP00000549459.1
	PAGE2B	ENST00000374974.7	TSL:5	c.247C>A	p.Leu83Ile	missense	Exon 4 of 5	ENSP00000364113.3	Q5JRL0

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD2 exomes AF: 0.0000218 AC: 4 AN: 183106 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000490

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000638 AC: 7 AN: 1097838 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 363322

African (AFR) AF: 0.00 AC: 0 AN: 26346

American (AMR) AF: 0.00 AC: 0 AN: 35191

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19379

East Asian (EAS) AF: 0.00 AC: 0 AN: 30196

South Asian (SAS) AF: 0.00 AC: 0 AN: 54102

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40506

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4130

European-Non Finnish (NFE) AF: 0.00000831 AC: 7 AN: 841913

Other (OTH) AF: 0.00 AC: 0 AN: 46075

GnomAD4 genome Cov.: 23

Alfa AF: 0.0000540 Hom.: 0

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	0.096
BayesDel_addAF	Benign	-0.62	T
BayesDel_noAF	Benign	-0.98
CADD	Benign	5.9
DANN	Benign	0.82
DEOGEN2	Benign	0.0059	T
FATHMM_MKL	Benign	0.0020	N
LIST_S2	Benign	0.62	T
M_CAP	Benign	0.0012	T
MetaRNN	Benign	0.079	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	0.69	N
PhyloP100		-0.24
PrimateAI	Benign	0.43	T
PROVEAN	Benign	-0.26	N
REVEL	Benign	0.011
Sift	Benign	0.048	D
Sift4G	Benign	0.22	T
Polyphen		0.12	B
Vest4		0.13
MutPred		0.27		Gain of methylation at K102 (P = 0.0811)
MVP		0.014
MPC		0.57
ClinPred		0.025	T
GERP RS		-1.9
Varity_R		0.087
gMVP		0.0025
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

dbSNP: rs781620826; hg19: chrX-55103936;