rs782070194

Variant names:

• chrX-135905333-C-A
• rs782070194
• NM_001381902.1:c.395C>A

Your query was ambiguous. Multiple possible variants found:

• chrX-135905333-C-A
• chrX-135905333-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001381902.1(SAGE1):​c.395C>A​(p.Pro132Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000183 in 1,095,153 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. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P132L) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 23)
  • Exomes 𝑓: 0.0000018 (0 hom. 0 hem.)
• Consequence: SAGE1 NM_001381902.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.20
• 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.120292604).

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.395C>A	p.Pro132Gln	missense	Exon 5 of 20	NP_001368831.1	Q9NXZ1
	SAGE1	NM_018666.3		c.395C>A	p.Pro132Gln	missense	Exon 5 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.395C>A	p.Pro132Gln	missense	Exon 5 of 20	ENSP00000359743.3	Q9NXZ1
	SAGE1	ENST00000324447.8	TSL:5	c.395C>A	p.Pro132Gln	missense	Exon 5 of 20	ENSP00000323191.3	Q9NXZ1

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome AF: 0.00000183 AC: 2 AN: 1095153 Hom.: 0 Cov.: 28 AF XY: 0.00 AC XY: 0 AN XY: 360663

African (AFR) AF: 0.00 AC: 0 AN: 26359

American (AMR) AF: 0.00 AC: 0 AN: 35183

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19344

East Asian (EAS) AF: 0.00 AC: 0 AN: 30186

South Asian (SAS) AF: 0.00 AC: 0 AN: 53809

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40480

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4130

European-Non Finnish (NFE) AF: 0.00000238 AC: 2 AN: 839674

Other (OTH) AF: 0.00 AC: 0 AN: 45988

GnomAD4 genome Cov.: 23

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.60
CADD	Benign	12
DANN	Benign	0.97
DEOGEN2	Benign	0.026	T
FATHMM_MKL	Benign	0.037	N
LIST_S2	Benign	0.29	T
M_CAP	Benign	0.0011	T
MetaRNN	Benign	0.12	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.6	L
PhyloP100		1.2
PrimateAI	Benign	0.35	T
PROVEAN	Benign	-1.7	N
REVEL	Benign	0.046
Sift	Uncertain	0.0020	D
Sift4G	Uncertain	0.0030	D
Polyphen		1.0	D
Vest4		0.29
MutPred		0.41		Loss of glycosylation at P132 (P = 0.0379)
MVP		0.18
ClinPred		0.25	T
GERP RS		1.1
Varity_R		0.070
gMVP		0.058
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: rs782070194; hg19: chrX-134987492;