chrX-49691373-C-T

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2

The NM_003785.4(PAGE1):​c.168G>A​(p.Gly56Gly) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00539 in 1,189,221 control chromosomes in the GnomAD database, including 16 homozygotes. There are 2,070 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0037 ( 1 hom., 114 hem., cov: 23)
Exomes 𝑓: 0.0056 ( 15 hom. 1956 hem. )

Consequence

PAGE1
NM_003785.4 splice_region, synonymous

Scores

2
Splicing: ADA: 0.00001910
2

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -1.86
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -17 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.87).
BP6
Variant X-49691373-C-T is Benign according to our data. Variant chrX-49691373-C-T is described in ClinVar as [Benign]. Clinvar id is 789252.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chrX-49691373-C-T is described in Lovd as [Likely_benign].
BP7
Synonymous conserved (PhyloP=-1.86 with no splicing effect.
BS2
High Hemizygotes in GnomAd4 at 114 gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
PAGE1NM_003785.4 linkc.168G>A p.Gly56Gly splice_region_variant, synonymous_variant Exon 4 of 6 ENST00000376150.4 NP_003776.2 O75459
PAGE1XM_011543998.3 linkc.168G>A p.Gly56Gly splice_region_variant, synonymous_variant Exon 4 of 6 XP_011542300.1 O75459

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
PAGE1ENST00000376150.4 linkc.168G>A p.Gly56Gly splice_region_variant, synonymous_variant Exon 4 of 6 1 NM_003785.4 ENSP00000365320.3 O75459

Frequencies

GnomAD3 genomes
AF:
0.00371
AC:
413
AN:
111449
Hom.:
1
Cov.:
23
AF XY:
0.00339
AC XY:
114
AN XY:
33669
show subpopulations
Gnomad AFR
AF:
0.000684
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00420
Gnomad ASJ
AF:
0.000378
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00191
Gnomad FIN
AF:
0.000503
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00637
Gnomad OTH
AF:
0.000670
GnomAD3 exomes
AF:
0.00348
AC:
589
AN:
169157
Hom.:
0
AF XY:
0.00373
AC XY:
212
AN XY:
56857
show subpopulations
Gnomad AFR exome
AF:
0.000938
Gnomad AMR exome
AF:
0.00187
Gnomad ASJ exome
AF:
0.000602
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00288
Gnomad FIN exome
AF:
0.000447
Gnomad NFE exome
AF:
0.00597
Gnomad OTH exome
AF:
0.00293
GnomAD4 exome
AF:
0.00557
AC:
6000
AN:
1077721
Hom.:
15
Cov.:
26
AF XY:
0.00565
AC XY:
1956
AN XY:
346501
show subpopulations
Gnomad4 AFR exome
AF:
0.000937
Gnomad4 AMR exome
AF:
0.00188
Gnomad4 ASJ exome
AF:
0.000430
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00270
Gnomad4 FIN exome
AF:
0.000945
Gnomad4 NFE exome
AF:
0.00666
Gnomad4 OTH exome
AF:
0.00420
GnomAD4 genome
AF:
0.00370
AC:
413
AN:
111500
Hom.:
1
Cov.:
23
AF XY:
0.00338
AC XY:
114
AN XY:
33730
show subpopulations
Gnomad4 AFR
AF:
0.000683
Gnomad4 AMR
AF:
0.00420
Gnomad4 ASJ
AF:
0.000378
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00192
Gnomad4 FIN
AF:
0.000503
Gnomad4 NFE
AF:
0.00637
Gnomad4 OTH
AF:
0.000661
Alfa
AF:
0.00515
Hom.:
212
Bravo
AF:
0.00346

ClinVar

Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not provided Benign:2
-
Breakthrough Genomics, Breakthrough Genomics
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: not provided

- -

Aug 09, 2017
Labcorp Genetics (formerly Invitae), Labcorp
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.87
CADD
Benign
0.35
DANN
Benign
0.30

Splicing

Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Benign
0.000019
dbscSNV1_RF
Benign
0.0
SpliceAI score (max)
0.050
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: rs145017650; hg19: chrX-49455976; API