X-55077503-C-T

Variant names:

• chrX-55077503-C-T
• rs781620826
• NM_001015038.3:c.298C>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.298C>T​(p.Leu100Phe) 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. 14/21 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. L100I) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 23)
• Consequence: PAGE2B NM_001015038.3 missense
• Clinical Significance: Not reported in ClinVar
• 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=0.074709326).

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>T	p.Leu100Phe	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>T	p.Leu100Phe	missense	Exon 4 of 5	ENSP00000364110.1	Q5JRK9
	PAGE2B	ENST00000879400.1		c.298C>T	p.Leu100Phe	missense	Exon 3 of 4	ENSP00000549459.1
	PAGE2B	ENST00000374974.7	TSL:5	c.247C>T	p.Leu83Phe	missense	Exon 4 of 5	ENSP00000364113.3	Q5JRL0

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 23

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.54	T
BayesDel_noAF	Benign	-1.0
CADD	Benign	7.6
DANN	Uncertain	0.98
DEOGEN2	Benign	0.010	T
FATHMM_MKL	Benign	0.0014	N
LIST_S2	Benign	0.66	T
M_CAP	Benign	0.0014	T
MetaRNN	Benign	0.075	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	0.69	N
PhyloP100		-0.24
PrimateAI	Benign	0.41	T
PROVEAN	Benign	-0.70	N
REVEL	Benign	0.015
Sift	Uncertain	0.022	D
Sift4G	Benign	0.22	T
Polyphen		0.48	P
Vest4		0.049
MutPred		0.32		Gain of catalytic residue at L100 (P = 0.0067)
MVP		0.040
MPC		0.89
ClinPred		0.18	T
GERP RS		-1.9
Varity_R		0.081
gMVP		0.0025
Mutation Taster		=97/3	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;