Genetic Variant SAGE1:p.Thr8Thr (chrX-135896266-G-A) – ACMG Classification: Benign (-14 pts)

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6BP7BA1

The NM_001381902.1(SAGE1):c.24G>A(p.Thr8Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.248 in 1,201,637 control chromosomes in the GnomAD database, including 26,515 homozygotes. There are 94,938 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.22 ( 2015 hom., 7119 hem., cov: 23)

Exomes 𝑓: 0.25 ( 24500 hom. 87819 hem. )

Consequence

SAGE1
NM_001381902.1 synonymous

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 1.03

Publications

6 publications found

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 was made for transcript

Our verdict: Benign. The variant received -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.91).

BP6

Variant X-135896266-G-A is Benign according to our data. Variant chrX-135896266-G-A is described in ClinVar as Benign. ClinVar VariationId is 3056169.Status of the report is no_assertion_criteria_provided, 0 stars.

BP7

Synonymous conserved (PhyloP=1.03 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.255 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001381902.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SAGE1	NM_001381902.1	MANE Select	c.24G>A	p.Thr8Thr	synonymous	Exon 2 of 20	NP_001368831.1	Q9NXZ1
	SAGE1	NM_018666.3		c.24G>A	p.Thr8Thr	synonymous	Exon 2 of 20	NP_061136.2	Q9NXZ1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SAGE1	ENST00000370709.4	TSL:5 MANE Select	c.24G>A	p.Thr8Thr	synonymous	Exon 2 of 20	ENSP00000359743.3	Q9NXZ1
	SAGE1	ENST00000324447.8	TSL:5	c.24G>A	p.Thr8Thr	synonymous	Exon 2 of 20	ENSP00000323191.3	Q9NXZ1

Frequencies

GnomAD3 genomes

AF:

0.215

AC:

23970

AN:

111409

Hom.:

2010

Cov.:

show subpopulations

Gnomad AFR

AF:

0.131

Gnomad AMI

AF:

0.359

Gnomad AMR

AF:

0.222

Gnomad ASJ

AF:

0.248

Gnomad EAS

AF:

0.127

Gnomad SAS

AF:

0.159

Gnomad FIN

AF:

0.304

Gnomad MID

AF:

0.179

Gnomad NFE

AF:

0.258

Gnomad OTH

AF:

0.211

GnomAD2 exomes

AF:

0.227

AC:

41568

AN:

182813

AF XY:

0.223

show subpopulations

Gnomad AFR exome

AF:

0.130

Gnomad AMR exome

AF:

0.229

Gnomad ASJ exome

AF:

0.253

Gnomad EAS exome

AF:

0.121

Gnomad FIN exome

AF:

0.324

Gnomad NFE exome

AF:

0.258

Gnomad OTH exome

AF:

0.220

GnomAD4 exome

AF:

0.251

AC:

273598

AN:

1090171

Hom.:

24500

Cov.:

AF XY:

0.245

AC XY:

87819

AN XY:

357999

show subpopulations

African (AFR)

AF:

0.125

AC:

3276

AN:

26271

American (AMR)

AF:

0.227

AC:

7978

AN:

35166

Ashkenazi Jewish (ASJ)

AF:

0.252

AC:

4872

AN:

19317

East Asian (EAS)

AF:

0.118

AC:

3569

AN:

30168

South Asian (SAS)

AF:

0.154

AC:

8289

AN:

53796

European-Finnish (FIN)

AF:

0.319

AC:

12887

AN:

40458

Middle Eastern (MID)

AF:

0.187

AC:

578

AN:

3087

European-Non Finnish (NFE)

AF:

0.265

AC:

221658

AN:

836111

Other (OTH)

AF:

0.229

AC:

10491

AN:

45797

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.459

Heterozygous variant carriers

6220

12440

18660

24880

31100

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

7796

15592

23388

31184

38980

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.215

AC:

23991

AN:

111466

Hom.:

2015

Cov.:

AF XY:

0.211

AC XY:

7119

AN XY:

33700

show subpopulations

African (AFR)

AF:

0.131

AC:

4050

AN:

30820

American (AMR)

AF:

0.223

AC:

2349

AN:

10555

Ashkenazi Jewish (ASJ)

AF:

0.248

AC:

657

AN:

2647

East Asian (EAS)

AF:

0.127

AC:

448

AN:

3536

South Asian (SAS)

AF:

0.160

AC:

427

AN:

2672

European-Finnish (FIN)

AF:

0.304

AC:

1786

AN:

5880

Middle Eastern (MID)

AF:

0.162

AC:

AN:

216

European-Non Finnish (NFE)

AF:

0.258

AC:

13675

AN:

52933

Other (OTH)

AF:

0.210

AC:

323

AN:

1535

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

680

1361

2041

2722

3402

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

250

500

750

1000

1250

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.240

Hom.:

2145

Bravo

AF:

0.210

ClinVar

ClinVar submissions

Significance:Benign

Revision:no assertion criteria provided

View on ClinVar

Pathogenic

VUS

Benign

Condition

SAGE1-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

3.5

(source)

DANN

Benign

0.28

PhyloP100

1.0

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over