chrX-49694736-C-T

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_003785.4(PAGE1):​c.35G>A​(p.Arg12Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000192 in 1,197,836 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 63 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000062 ( 0 hom., 1 hem., cov: 23)
Exomes 𝑓: 0.00021 ( 0 hom. 62 hem. )

Consequence

PAGE1
NM_003785.4 missense

Scores

1
16

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.908
Variant links:
Genes affected
PAGE1 (HGNC:4107): (PAGE family member 1) This gene belongs to a family of genes that are expressed in a variety of tumors but not in normal tissues, except for the testis. Unlike the other gene family members, this gene does not encode an antigenic peptide. Nothing is presently known about the function of this protein. [provided by RefSeq, Jul 2008]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.062268823).
BS2
High Hemizygotes in GnomAdExome4 at 62 gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
PAGE1NM_003785.4 linkc.35G>A p.Arg12Lys missense_variant Exon 2 of 6 ENST00000376150.4 NP_003776.2 O75459
PAGE1XM_011543998.3 linkc.35G>A p.Arg12Lys missense_variant Exon 2 of 6 XP_011542300.1 O75459

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
PAGE1ENST00000376150.4 linkc.35G>A p.Arg12Lys missense_variant Exon 2 of 6 1 NM_003785.4 ENSP00000365320.3 O75459

Frequencies

GnomAD3 genomes
AF:
0.0000624
AC:
7
AN:
112248
Hom.:
0
Cov.:
23
AF XY:
0.0000291
AC XY:
1
AN XY:
34414
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000131
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000897
AC:
16
AN:
178349
Hom.:
0
AF XY:
0.0000635
AC XY:
4
AN XY:
62963
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.0000628
Gnomad NFE exome
AF:
0.000161
Gnomad OTH exome
AF:
0.000453
GnomAD4 exome
AF:
0.000205
AC:
223
AN:
1085588
Hom.:
0
Cov.:
24
AF XY:
0.000176
AC XY:
62
AN XY:
351838
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.0000741
Gnomad4 NFE exome
AF:
0.000242
Gnomad4 OTH exome
AF:
0.000416
GnomAD4 genome
AF:
0.0000624
AC:
7
AN:
112248
Hom.:
0
Cov.:
23
AF XY:
0.0000291
AC XY:
1
AN XY:
34414
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000131
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000712
Hom.:
0
Bravo
AF:
0.0000793
TwinsUK
AF:
0.000270
AC:
1
ALSPAC
AF:
0.00
AC:
0
ExAC
AF:
0.0000412
AC:
5

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Dec 12, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.35G>A (p.R12K) alteration is located in exon 2 (coding exon 1) of the PAGE1 gene. This alteration results from a G to A substitution at nucleotide position 35, causing the arginine (R) at amino acid position 12 to be replaced by a lysine (K). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.16
BayesDel_addAF
Benign
-0.69
T
BayesDel_noAF
Benign
-0.98
CADD
Benign
0.38
DANN
Benign
0.60
DEOGEN2
Benign
0.012
T
FATHMM_MKL
Benign
0.0021
N
LIST_S2
Benign
0.36
T
M_CAP
Benign
0.0011
T
MetaRNN
Benign
0.062
T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
1.7
L
PrimateAI
Benign
0.35
T
PROVEAN
Benign
-1.4
N
REVEL
Benign
0.032
Sift
Uncertain
0.025
D
Sift4G
Benign
0.10
T
Polyphen
0.048
B
Vest4
0.082
MVP
0.030
MPC
0.22
ClinPred
0.016
T
GERP RS
-1.3
Varity_R
0.15
gMVP
0.050

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs782044654; hg19: chrX-49459339; API