X-135905354-C-T

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_001381902.1(SAGE1):​c.416C>T​(p.Ala139Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000913 in 1,095,589 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 6 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 23)
Exomes 𝑓: 0.0000091 ( 0 hom. 6 hem. )

Consequence

SAGE1
NM_001381902.1 missense

Scores

1
16

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.20
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 Likely_benign. Variant got -6 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.122632384).
BS2
High Hemizygotes in GnomAdExome4 at 6 gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SAGE1NM_001381902.1 linkc.416C>T p.Ala139Val missense_variant Exon 5 of 20 ENST00000370709.4 NP_001368831.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
SAGE1ENST00000370709.4 linkc.416C>T p.Ala139Val missense_variant Exon 5 of 20 5 NM_001381902.1 ENSP00000359743.3 Q9NXZ1
SAGE1ENST00000324447.8 linkc.416C>T p.Ala139Val missense_variant Exon 5 of 20 5 ENSP00000323191.3 Q9NXZ1

Frequencies

GnomAD3 genomes
Cov.:
23
GnomAD4 exome
AF:
0.00000913
AC:
10
AN:
1095589
Hom.:
0
Cov.:
28
AF XY:
0.0000166
AC XY:
6
AN XY:
361067
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:
0.000167
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.0000217
GnomAD4 genome
Cov.:
23
Bravo
AF:
0.00000756

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Jan 23, 2023
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.416C>T (p.A139V) alteration is located in exon 5 (coding exon 4) of the SAGE1 gene. This alteration results from a C to T substitution at nucleotide position 416, causing the alanine (A) at amino acid position 139 to be replaced by a valine (V). 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
0.24
BayesDel_addAF
Benign
-0.34
T
BayesDel_noAF
Benign
-0.73
CADD
Benign
16
DANN
Uncertain
1.0
DEOGEN2
Benign
0.0081
T;T;T
FATHMM_MKL
Benign
0.031
N
LIST_S2
Benign
0.49
T;T;.
M_CAP
Benign
0.0018
T
MetaRNN
Benign
0.12
T;T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
1.0
L;.;L
PrimateAI
Benign
0.38
T
PROVEAN
Benign
-0.29
N;N;N
REVEL
Benign
0.047
Sift
Benign
0.087
T;T;T
Sift4G
Benign
0.79
T;T;T
Polyphen
0.97
D;P;D
Vest4
0.26
MutPred
0.34
Gain of catalytic residue at A139 (P = 0.0401);Gain of catalytic residue at A139 (P = 0.0401);Gain of catalytic residue at A139 (P = 0.0401);
MVP
0.27
ClinPred
0.19
T
GERP RS
1.1
Varity_R
0.053
gMVP
0.038

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: rs2088767955; hg19: chrX-134987513; API