rs4826381

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chrX-55263341-T-C
• chrX-55263341-T-G

Variant summary

Our verdict is Likely benign. The variant received -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. 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.

• 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
• 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: Likely_benign. The variant received -4 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PAGE3	NM_001017931.3	c.103A>G	p.Asn35Asp	missense_variant	Exon 3 of 5	ENST00000374951.6	NP_001017931.3
PAGE3	NM_001171252.2	c.103A>G	p.Asn35Asp	missense_variant	Exon 3 of 5		NP_001164723.2
PAGE3	NM_001303613.2	c.103A>G	p.Asn35Asp	missense_variant	Exon 3 of 5		NP_001290542.2
PAGE3	XM_017029282.3	c.103A>G	p.Asn35Asp	missense_variant	Exon 3 of 5		XP_016884771.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PAGE3	ENST00000374951.6	c.103A>G	p.Asn35Asp	missense_variant	Exon 3 of 5	1	NM_001017931.3	ENSP00000364089.1
PAGE3	ENST00000519203.1	c.103A>G	p.Asn35Asp	missense_variant	Exon 3 of 5	1		ENSP00000429571.1

Frequencies

GnomAD3 genomes AF: 0.841 AC: 92285 AN: 109678 Hom.: 28891 Cov.: 22

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

GnomAD2 exomes AF: 0.934 AC: 169359 AN: 181367 AF XY: 0.944

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 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

African (AFR) AF: 0.521 AC: 7285 AN: 13973

American (AMR) AF: 0.957 AC: 32879 AN: 34345

Ashkenazi Jewish (ASJ) AF: 0.921 AC: 14172 AN: 15384

East Asian (EAS) AF: 1.00 AC: 27151 AN: 27154

South Asian (SAS) AF: 0.929 AC: 39018 AN: 42018

European-Finnish (FIN) AF: 0.992 AC: 39932 AN: 40240

Middle Eastern (MID) AF: 0.800 AC: 2423 AN: 3029

European-Non Finnish (NFE) AF: 0.969 AC: 247970 AN: 255840

Other (OTH) AF: 0.923 AC: 22962 AN: 24886

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

African (AFR) AF: 0.523 AC: 15754 AN: 30143

American (AMR) AF: 0.922 AC: 9302 AN: 10092

Ashkenazi Jewish (ASJ) AF: 0.930 AC: 2454 AN: 2638

East Asian (EAS) AF: 1.00 AC: 3523 AN: 3523

South Asian (SAS) AF: 0.926 AC: 2319 AN: 2505

European-Finnish (FIN) AF: 0.993 AC: 5629 AN: 5668

Middle Eastern (MID) AF: 0.806 AC: 174 AN: 216

European-Non Finnish (NFE) AF: 0.970 AC: 51216 AN: 52799

Other (OTH) AF: 0.858 AC: 1269 AN: 1479

Alfa AF: 0.916 Hom.: 77378

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
PhyloP100		-0.12
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
Mutation Taster		=100/0	polymorphism (auto)

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; COSMIC: COSV107495176;