rs1229227582

Variant names:

• chrX-135906419-G-A
• rs1229227582
• NM_001381902.1:c.604G>A

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_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. 15/21 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
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.522
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.021223992).

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.604G>A	p.Val202Ile	missense	Exon 7 of 20	NP_001368831.1	Q9NXZ1
	SAGE1	NM_018666.3		c.604G>A	p.Val202Ile	missense	Exon 7 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.604G>A	p.Val202Ile	missense	Exon 7 of 20	ENSP00000359743.3	Q9NXZ1
	SAGE1	ENST00000324447.8	TSL:5	c.604G>A	p.Val202Ile	missense	Exon 7 of 20	ENSP00000323191.3	Q9NXZ1

Frequencies

GnomAD3 genomes AF: 0.0000266 AC: 3 AN: 112595 Hom.: 0 Cov.: 28

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

GnomAD2 exomes AF: 0.0000167 AC: 3 AN: 179519 AF XY: 0.00

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 FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000356 AC: 39 AN: 1096155 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 361665

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 26320

American (AMR) AF: 0.00 AC: 0 AN: 34967

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19295

East Asian (EAS) AF: 0.00 AC: 0 AN: 30168

South Asian (SAS) AF: 0.000692 AC: 37 AN: 53504

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40504

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4120

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 841256

Other (OTH) AF: 0.0000435 AC: 2 AN: 46021

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.0000266 AC: 3 AN: 112650 Hom.: 0 Cov.: 28 AF XY: 0.00 AC XY: 0 AN XY: 34828

African (AFR) AF: 0.00 AC: 0 AN: 31029

American (AMR) AF: 0.00 AC: 0 AN: 10627

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2651

East Asian (EAS) AF: 0.00 AC: 0 AN: 3577

South Asian (SAS) AF: 0.00110 AC: 3 AN: 2721

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6294

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 217

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 53306

Other (OTH) AF: 0.00 AC: 0 AN: 1537

Alfa AF: 0.00 Hom.: 0

ExAC AF: 0.0000412 AC: 5

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.67	T
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.12
DANN	Benign	0.19
DEOGEN2	Benign	0.0060	T
FATHMM_MKL	Benign	0.022	N
LIST_S2	Benign	0.38	T
M_CAP	Benign	0.0019	T
MetaRNN	Benign	0.021	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	0.20	N
PhyloP100		0.52
PrimateAI	Benign	0.40	T
PROVEAN	Benign	0.32	N
REVEL	Benign	0.012
Sift	Benign	0.73	T
Sift4G	Benign	1.0	T
Polyphen		0.035	B
Vest4		0.24
MutPred		0.33		Gain of helix (P = 0.0425)
MVP		0.099
ClinPred		0.015	T
GERP RS		0.34
Varity_R		0.030
gMVP		0.0073
Mutation Taster		=99/1	polymorphism

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

Other links and lift over

dbSNP: rs1229227582; hg19: chrX-134988578;