X-55263341-T-G

Variant names:

• chrX-55263341-T-G
• rs4826381
• NM_001017931.3:c.103A>C

Variant summary

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

The NM_001017931.3(PAGE3):​c.103A>C​(p.Asn35His) 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. 14/19 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 22)
• Consequence: PAGE3 NM_001017931.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.122
• Publications: 12 publications found

Genes affected

PAGE3 (HGNC:4110): (PAGE family member 3) This gene is a member of family of proteins that are expressed in a variety of tumors and in some fetal and reproductive tissues. Multiple alternatively spliced transcript variants have been observed. [provided by RefSeq, Jan 2015]

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=0.08934644).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001017931.3. 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
	PAGE3	NM_001017931.3	MANE Select	c.103A>C	p.Asn35His	missense	Exon 3 of 5	NP_001017931.3	Q5JUK9
	PAGE3	NM_001171252.2		c.103A>C	p.Asn35His	missense	Exon 3 of 5	NP_001164723.2	Q5JUK9
	PAGE3	NM_001303613.2		c.103A>C	p.Asn35His	missense	Exon 3 of 5	NP_001290542.2	Q5JUK9

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PAGE3	ENST00000374951.6	TSL:1 MANE Select	c.103A>C	p.Asn35His	missense	Exon 3 of 5	ENSP00000364089.1	Q5JUK9
	PAGE3	ENST00000519203.1	TSL:1	c.103A>C	p.Asn35His	missense	Exon 3 of 5	ENSP00000429571.1	Q5JUK9

Frequencies

GnomAD3 genomes Cov.: 22

GnomAD4 exome Cov.: 0

GnomAD4 genome Cov.: 22

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.082
BayesDel_addAF	Benign	-0.56	T
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.6
DANN	Benign	0.83
DEOGEN2	Benign	0.010	T
FATHMM_MKL	Benign	0.0036	N
LIST_S2	Benign	0.23	T
M_CAP	Benign	0.00093	T
MetaRNN	Benign	0.089	T
MetaSVM	Benign	-0.95	T
PhyloP100		-0.12
PrimateAI	Benign	0.38	T
PROVEAN	Benign	-1.4	N
REVEL	Benign	0.016
Sift	Benign	0.11	T
Sift4G	Benign	0.14	T
Polyphen		0.0020	B
Vest4		0.15
MutPred		0.36		Loss of stability (P = 0.0576)
MVP		0.19
MPC		0.0052
ClinPred		0.036	T
GERP RS		1.1
Varity_R		0.059
gMVP		0.015
Mutation Taster		=100/0	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: rs4826381; hg19: chrX-55289774;