NM_001381902.1:c.607A>G

Variant names:

• chrX-135906422-A-G
• rs145404090
• NM_001381902.1:c.607A>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001381902.1(SAGE1):​c.607A>G​(p.Thr203Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000612 in 1,208,412 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 0.00051 (0 hom., 0 hem., cov: 28)
  • Exomes 𝑓: 0.00062 (0 hom. 0 hem.)
• Consequence: SAGE1 NM_001381902.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1 B:2
• Conservation: PhyloP100: 0.252
• Publications: 4 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 -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.077819765).

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.607A>G	p.Thr203Ala	missense	Exon 7 of 20	NP_001368831.1	Q9NXZ1
	SAGE1	NM_018666.3		c.607A>G	p.Thr203Ala	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.607A>G	p.Thr203Ala	missense	Exon 7 of 20	ENSP00000359743.3	Q9NXZ1
	SAGE1	ENST00000324447.8	TSL:5	c.607A>G	p.Thr203Ala	missense	Exon 7 of 20	ENSP00000323191.3	Q9NXZ1

Frequencies

GnomAD3 genomes AF: 0.000506 AC: 57 AN: 112561 Hom.: 0 Cov.: 28

Gnomad AFR AF: 0.000194

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: 0.000957

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000439 AC: 79 AN: 179912 AF XY: 0.00

Gnomad AFR exome AF: 0.000229

Gnomad AMR exome AF: 0.0000745

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000188

Gnomad NFE exome AF: 0.000867

Gnomad OTH exome AF: 0.000225

GnomAD4 exome AF: 0.000622 AC: 682 AN: 1095797 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 361445

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

African (AFR) AF: 0.000114 AC: 3 AN: 26325

American (AMR) AF: 0.0000572 AC: 2 AN: 34973

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19302

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

South Asian (SAS) AF: 0.00 AC: 0 AN: 53570

European-Finnish (FIN) AF: 0.000247 AC: 10 AN: 40501

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4124

European-Non Finnish (NFE) AF: 0.000773 AC: 650 AN: 840828

Other (OTH) AF: 0.000370 AC: 17 AN: 46006

⚠️ 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: 0.000506 AC: 57 AN: 112615 Hom.: 0 Cov.: 28 AF XY: 0.00 AC XY: 0 AN XY: 34801

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

African (AFR) AF: 0.000194 AC: 6 AN: 31005

American (AMR) AF: 0.00 AC: 0 AN: 10628

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2649

East Asian (EAS) AF: 0.00 AC: 0 AN: 3585

South Asian (SAS) AF: 0.00 AC: 0 AN: 2724

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6299

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 218

European-Non Finnish (NFE) AF: 0.000957 AC: 51 AN: 53272

Other (OTH) AF: 0.00 AC: 0 AN: 1544

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.000198 Hom.: 0

ESP6500AA AF: 0.000261 AC: 1

ESP6500EA AF: 0.000595 AC: 4

ExAC AF: 0.000675 AC: 82

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Benign	-0.61	T
BayesDel_noAF	Benign	-0.72
CADD	Benign	7.8
DANN	Benign	0.97
DEOGEN2	Benign	0.074	T
FATHMM_MKL	Benign	0.023	N
LIST_S2	Benign	0.29	T
M_CAP	Benign	0.0038	T
MetaRNN	Benign	0.078	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.6	L
PhyloP100		0.25
PrimateAI	Benign	0.40	T
PROVEAN	Benign	-2.2	N
REVEL	Benign	0.053
Sift	Benign	0.051	T
Sift4G	Uncertain	0.011	D
Polyphen		0.98	D
Vest4		0.34
MVP		0.37
ClinPred		0.026	T
GERP RS		1.3
Varity_R		0.092
gMVP		0.027
Mutation Taster		=100/0	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: rs145404090; hg19: chrX-134988581;