Genetic Variant SAGE1:p.His157GlnfsTer5 (chrX-135906038-C-CA) – ACMG Classification: Likely_benign (-5 pts)

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP6BS2

The NM_001381902.1(SAGE1):c.470dupA(p.His157GlnfsTer5) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000311 in 1,204,946 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 115 hemizygotes in GnomAD. Variant has been reported in ClinVar as Likely benign (no stars). Variant results in nonsense mediated mRNA decay.

Frequency

Genomes: 𝑓 0.00027 ( 0 hom., 8 hem., cov: 23)

Exomes 𝑓: 0.00032 ( 0 hom. 107 hem. )

Consequence

SAGE1
NM_001381902.1 frameshift

Scores

Not classified

Clinical Significance

Likely benign no assertion criteria provided B:3

Conservation

PhyloP100: 1.52

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:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -5 ACMG points.

BP6

Variant X-135906038-C-CA is Benign according to our data. Variant chrX-135906038-C-CA is described in ClinVar as [Likely_benign]. Clinvar id is 1206116.Status of the report is no_assertion_criteria_provided, 0 stars.

BS2

High Hemizygotes in GnomAd4 at 8 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SAGE1	NM_001381902.1 link	c.470dupA	p.His157GlnfsTer5	frameshift_variant	Exon 6 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.470dupA	p.His157GlnfsTer5	frameshift_variant	Exon 6 of 20	5	NM_001381902.1	ENSP00000359743.3		Q9NXZ1
SAGE1	ENST00000324447.8 link	c.470dupA	p.His157GlnfsTer5	frameshift_variant	Exon 6 of 20	5		ENSP00000323191.3		Q9NXZ1

Frequencies

GnomAD3 genomes

AF:

0.000270

AC:

AN:

111097

Hom.:

Cov.:

AF XY:

0.000240

AC XY:

AN XY:

33317

show subpopulations

Gnomad AFR

AF:

0.0000328

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:

0.000509

Gnomad OTH

AF:

0.00135

GnomAD3 exomes

AF:

0.000179

AC:

AN:

178541

Hom.:

AF XY:

0.000221

AC XY:

AN XY:

63269

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:

0.0000632

Gnomad NFE exome

AF:

0.000375

Gnomad OTH exome

AF:

0.000228

GnomAD4 exome

AF:

0.000315

AC:

345

AN:

1093849

Hom.:

Cov.:

AF XY:

0.000298

AC XY:

107

AN XY:

359507

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:

0.0000742

Gnomad4 NFE exome

AF:

0.000403

Gnomad4 OTH exome

AF:

0.0000871

GnomAD4 genome

AF:

0.000270

AC:

AN:

111097

Hom.:

Cov.:

AF XY:

0.000240

AC XY:

AN XY:

33317

show subpopulations

Gnomad4 AFR

AF:

0.0000328

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:

0.000509

Gnomad4 OTH

AF:

0.00135

Alfa

AF:

0.000489

Hom.:

Bravo

AF:

0.000276

ClinVar

Significance: Likely benign

Submissions summary: Benign:3

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

not provided

Benign:2

Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

SAGE1-related disorder

Benign:1

Jun 06, 2021

PreventionGenetics, part of Exact Sciences

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as likely 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

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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