X-55263341-T-C

Position:

• chrX-55263341-T-C

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001017931.3(PAGE3):​c.103A>G​(p.Asn35Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 12/17 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 nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.84 (28884 hom., 27106 hem., cov: 22)
  • Exomes 𝑓: 0.95 (129890 hom. 162376 hem.)
  • Failed GnomAD Quality Control
• 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 Likely_benign. Variant got -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=1.34829115E-5).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PAGE3	NM_001017931.3	c.103A>G	p.Asn35Asp	missense_variant	3/5	ENST00000374951.6
PAGE3	NM_001171252.2	c.103A>G	p.Asn35Asp	missense_variant	3/5
PAGE3	NM_001303613.2	c.103A>G	p.Asn35Asp	missense_variant	3/5
PAGE3	XM_017029282.3	c.103A>G	p.Asn35Asp	missense_variant	3/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PAGE3	ENST00000374951.6	c.103A>G	p.Asn35Asp	missense_variant	3/5	1	NM_001017931.3	P1
PAGE3	ENST00000519203.1	c.103A>G	p.Asn35Asp	missense_variant	3/5	1		P1

Frequencies

GnomAD3 genomes AF: 0.841 AC: 92285 AN: 109678 Hom.: 28891 Cov.: 22 AF XY: 0.847 AC XY: 27064 AN XY: 31952

Gnomad AFR AF: 0.523

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.922

Gnomad ASJ AF: 0.930

Gnomad EAS AF: 1.00

Gnomad SAS AF: 0.926

Gnomad FIN AF: 0.993

Gnomad MID AF: 0.801

Gnomad NFE AF: 0.970

Gnomad OTH AF: 0.856

GnomAD3 exomes AF: 0.934 AC: 169359 AN: 181367 Hom.: 50724 AF XY: 0.944 AC XY: 62158 AN XY: 65875

Gnomad AFR exome AF: 0.516

Gnomad AMR exome AF: 0.962

Gnomad ASJ exome AF: 0.924

Gnomad EAS exome AF: 1.00

Gnomad SAS exome AF: 0.930

Gnomad FIN exome AF: 0.993

Gnomad NFE exome AF: 0.969

Gnomad OTH exome AF: 0.949

GnomAD4 exome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.949 AC: 433792 AN: 456869 Hom.: 129890 Cov.: 0 AF XY: 0.951 AC XY: 162376 AN XY: 170659

Gnomad4 AFR exome AF: 0.521

Gnomad4 AMR exome AF: 0.957

Gnomad4 ASJ exome AF: 0.921

Gnomad4 EAS exome AF: 1.00

Gnomad4 SAS exome AF: 0.929

Gnomad4 FIN exome AF: 0.992

Gnomad4 NFE exome AF: 0.969

Gnomad4 OTH exome AF: 0.923

GnomAD4 genome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.841 AC: 92312 AN: 109735 Hom.: 28884 Cov.: 22 AF XY: 0.847 AC XY: 27106 AN XY: 32019

Gnomad4 AFR AF: 0.523

Gnomad4 AMR AF: 0.922

Gnomad4 ASJ AF: 0.930

Gnomad4 EAS AF: 1.00

Gnomad4 SAS AF: 0.926

Gnomad4 FIN AF: 0.993

Gnomad4 NFE AF: 0.970

Gnomad4 OTH AF: 0.858

Alfa AF: 0.932 Hom.: 60979

Bravo AF: 0.824

TwinsUK AF: 0.978 AC: 3628

ALSPAC AF: 0.979 AC: 2828

ESP6500AA AF: 0.531 AC: 2036

ESP6500EA AF: 0.968 AC: 6514

ExAC AF: 0.926 AC: 112375

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.051
BayesDel_addAF	Benign	-1.1	T
BayesDel_noAF	Benign	-1.2
CADD	Benign	0.19
DANN	Benign	0.15
DEOGEN2	Benign	0.0010	T;T
FATHMM_MKL	Benign	0.00011	N
LIST_S2	Benign	0.18	.;T
MetaRNN	Benign	0.000013	T;T
MetaSVM	Benign	-1.0	T
MutationTaster	Benign	1.0	P;P
PrimateAI	Benign	0.36	T
PROVEAN	Benign	1.8	N;N
REVEL	Benign	0.012
Sift	Benign	0.98	T;T
Sift4G	Benign	0.81	T;T
Polyphen		0.0	B;B
Vest4		0.036
MPC		0.0049
ClinPred		0.000016	T
GERP RS		1.1
Varity_R		0.056
gMVP		0.0055

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;