X-55263341-T-G

Position:

• chrX-55263341-T-G

Variant summary

Our verdict is Uncertain significance. Variant got 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. 13/18 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. N35D) has been classified as Likely benign.

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

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

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.08934644).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PAGE3	NM_001017931.3	c.103A>C	p.Asn35His	missense_variant	3/5	ENST00000374951.6	NP_001017931.3
PAGE3	NM_001171252.2	c.103A>C	p.Asn35His	missense_variant	3/5		NP_001164723.2
PAGE3	NM_001303613.2	c.103A>C	p.Asn35His	missense_variant	3/5		NP_001290542.2
PAGE3	XM_017029282.3	c.103A>C	p.Asn35His	missense_variant	3/5		XP_016884771.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PAGE3	ENST00000374951.6	c.103A>C	p.Asn35His	missense_variant	3/5	1	NM_001017931.3	ENSP00000364089.1
PAGE3	ENST00000519203.1	c.103A>C	p.Asn35His	missense_variant	3/5	1		ENSP00000429571.1

Frequencies

GnomAD3 genomes Cov.: 22

GnomAD4 exome Cov.: 0

GnomAD4 genome Cov.: 22

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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;T
FATHMM_MKL	Benign	0.0036	N
LIST_S2	Benign	0.23	.;T
M_CAP	Benign	0.00093	T
MetaRNN	Benign	0.089	T;T
MetaSVM	Benign	-0.95	T
PrimateAI	Benign	0.38	T
PROVEAN	Benign	-1.4	N;N
REVEL	Benign	0.016
Sift	Benign	0.11	T;T
Sift4G	Benign	0.14	T;T
Polyphen		0.0020	B;B
Vest4		0.15
MutPred		0.36		Loss of stability (P = 0.0576);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

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

Publications

LitVar

Other links and lift over

dbSNP: rs4826381; hg19: chrX-55289774;