X-135896274-C-T

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2

The NM_001381902.1(SAGE1):​c.32C>T​(p.Pro11Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000237 in 1,204,401 control chromosomes in the GnomAD database, including 2 homozygotes. There are 91 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.00033 ( 0 hom., 13 hem., cov: 23)
Exomes 𝑓: 0.00023 ( 2 hom. 78 hem. )

Consequence

SAGE1
NM_001381902.1 missense

Scores

17

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 0.583
Variant links:
Genes affected
SAGE1 (HGNC:30369): (sarcoma antigen 1) This gene belongs to a class of genes that are activated in tumors. These genes are expressed in tumors of different histologic types but not in normal tissues, except for spermatogenic cells and, for some, placenta. The proteins encoded by these genes appear to be strictly tumor specific, and hence may be excellent sources of antigens for cancer immunotherapy. This gene is expressed in sarcomas. [provided by RefSeq, Jul 2008]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.0044519603).
BP6
Variant X-135896274-C-T is Benign according to our data. Variant chrX-135896274-C-T is described in ClinVar as [Benign]. Clinvar id is 3059017.Status of the report is no_assertion_criteria_provided, 0 stars.
BS2
High Hemizygotes in GnomAd4 at 13 gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SAGE1NM_001381902.1 linkc.32C>T p.Pro11Leu missense_variant Exon 2 of 20 ENST00000370709.4 NP_001368831.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
SAGE1ENST00000370709.4 linkc.32C>T p.Pro11Leu missense_variant Exon 2 of 20 5 NM_001381902.1 ENSP00000359743.3 Q9NXZ1
SAGE1ENST00000324447.8 linkc.32C>T p.Pro11Leu missense_variant Exon 2 of 20 5 ENSP00000323191.3 Q9NXZ1

Frequencies

GnomAD3 genomes
AF:
0.000330
AC:
37
AN:
112065
Hom.:
0
Cov.:
23
AF XY:
0.000380
AC XY:
13
AN XY:
34255
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:
0.0103
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.000797
AC:
146
AN:
183133
Hom.:
1
AF XY:
0.000725
AC XY:
49
AN XY:
67607
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.0105
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.000221
GnomAD4 exome
AF:
0.000228
AC:
249
AN:
1092282
Hom.:
2
Cov.:
27
AF XY:
0.000218
AC XY:
78
AN XY:
358598
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00802
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.000131
GnomAD4 genome
AF:
0.000330
AC:
37
AN:
112119
Hom.:
0
Cov.:
23
AF XY:
0.000379
AC XY:
13
AN XY:
34319
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.0104
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000625
Hom.:
8
Bravo
AF:
0.000548
ExAC
AF:
0.000659
AC:
80

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: no assertion criteria provided
LINK: link

Submissions by phenotype

SAGE1-related disorder Benign:1
Apr 16, 2019
PreventionGenetics, part of Exact Sciences
Significance: Benign
Review Status: no assertion criteria provided
Collection Method: clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.088
BayesDel_addAF
Benign
-0.74
T
BayesDel_noAF
Benign
-0.83
CADD
Benign
3.5
DANN
Benign
0.48
DEOGEN2
Benign
0.0084
T;T;T
FATHMM_MKL
Benign
0.095
N
LIST_S2
Benign
0.48
T;T;.
M_CAP
Benign
0.0082
T
MetaRNN
Benign
0.0045
T;T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
0.20
N;.;N
PrimateAI
Benign
0.35
T
PROVEAN
Benign
-1.2
N;N;N
REVEL
Benign
0.074
Sift
Benign
0.23
T;T;T
Sift4G
Benign
0.34
T;T;T
Polyphen
0.0
B;B;B
Vest4
0.27
MVP
0.030
ClinPred
0.026
T
GERP RS
-0.36
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1
Varity_R
0.032
gMVP
0.0063

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: rs200108643; hg19: chrX-134978433; API