Genetic Variant SAGE1:p.Val202Ile (chrX-135906419-G-A) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001381902.1(SAGE1):c.604G>A(p.Val202Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000347 in 1,208,805 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples 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 0.000027 ( 0 hom., 0 hem., cov: 28)

Exomes 𝑓: 0.000036 ( 0 hom. 0 hem. )

Consequence

SAGE1
NM_001381902.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.522

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]

SAGE1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.021223992).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SAGE1	NM_001381902.1 link	c.604G>A	p.Val202Ile	missense_variant	Exon 7 of 20	ENST00000370709.4	NP_001368831.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SAGE1	ENST00000370709.4 link	c.604G>A	p.Val202Ile	missense_variant	Exon 7 of 20	5	NM_001381902.1	ENSP00000359743.3		Q9NXZ1
SAGE1	ENST00000324447.8 link	c.604G>A	p.Val202Ile	missense_variant	Exon 7 of 20	5		ENSP00000323191.3		Q9NXZ1

Frequencies

GnomAD3 genomes

AF:

0.0000266

AC:

AN:

112595

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

34763

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:

0.00110

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000167

AC:

AN:

179519

Hom.:

AF XY:

0.00

AC XY:

AN XY:

64165

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:

0.000169

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000356

AC:

AN:

1096155

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

361665

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:

0.000692

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000435

GnomAD4 genome

AF:

0.0000266

AC:

AN:

112650

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

34828

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:

0.00110

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

ExAC

AF:

0.0000412

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Feb 26, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.604G>A (p.V202I) alteration is located in exon 7 (coding exon 6) of the SAGE1 gene. This alteration results from a G to A substitution at nucleotide position 604, causing the valine (V) at amino acid position 202 to be replaced by an isoleucine (I). 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

0.10

BayesDel_addAF

Benign

-0.67

BayesDel_noAF

Benign

-0.94

CADD

Benign

0.12

DANN

Benign

0.19

DEOGEN2

Benign

0.0060

T;T

FATHMM_MKL

Benign

0.022

LIST_S2

Benign

0.38

T;.

M_CAP

Benign

0.0019

MetaRNN

Benign

0.021

T;T

MetaSVM

Benign

-0.98

MutationAssessor

Benign

0.20

N;N

PrimateAI

Benign

0.40

PROVEAN

Benign

0.32

N;N

REVEL

Benign

0.012

Sift

Benign

0.73

T;T

Sift4G

Benign

1.0

T;T

Polyphen

0.035

B;B

Vest4

0.24

MutPred

0.33

Gain of helix (P = 0.0425);Gain of helix (P = 0.0425);

MVP

0.099

ClinPred

0.015

GERP RS

0.34

Varity_R

0.030

gMVP

0.0073

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over