X-49317261-C-A

Variant names:

• chrX-49317261-C-A
• rs782659658
• NM_001098413.4:c.301C>A

Variant summary

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

The NM_001098413.4(GAGE10):​c.301C>A​(p.Pro101Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000914 in 1,094,125 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 1 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 22)
  • Exomes 𝑓: 9.1e-7 (0 hom. 1 hem.)
• Consequence: GAGE10 NM_001098413.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.103
• Publications: 0 publications found

Genes affected

GAGE10 (HGNC:30968): (G antigen 10)

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=0.09311211).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001098413.4. 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
	GAGE10	NM_001098413.4	MANE Select	c.301C>A	p.Pro101Thr	missense	Exon 4 of 5	NP_001091883.3	A6NGK3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GAGE10	ENST00000407599.4	TSL:5 MANE Select	c.301C>A	p.Pro101Thr	missense	Exon 4 of 5	ENSP00000385415.3	A6NGK3

Frequencies

GnomAD3 genomes Cov.: 22

GnomAD2 exomes AF: 0.00000545 AC: 1 AN: 183379 AF XY: 0.0000147

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: 0.0000122

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 9.14e-7 AC: 1 AN: 1094125 Hom.: 0 Cov.: 30 AF XY: 0.00000278 AC XY: 1 AN XY: 360233

African (AFR) AF: 0.00 AC: 0 AN: 26308

American (AMR) AF: 0.00 AC: 0 AN: 35069

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19249

East Asian (EAS) AF: 0.00 AC: 0 AN: 30039

South Asian (SAS) AF: 0.00 AC: 0 AN: 54096

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 39873

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4114

European-Non Finnish (NFE) AF: 0.00000119 AC: 1 AN: 839543

Other (OTH) AF: 0.00 AC: 0 AN: 45834

GnomAD4 genome Cov.: 22

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ExAC AF: 0.0000165 AC: 2

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	0.087
BayesDel_addAF	Benign	-0.49	T
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.70
DANN	Uncertain	0.98
FATHMM_MKL	Benign	0.014	N
M_CAP	Benign	0.00080	T
MetaRNN	Benign	0.093	T
MetaSVM	Benign	-1.0	T
PhyloP100		0.10
PrimateAI	Benign	0.24	T
PROVEAN	Benign	-1.4	N
REVEL	Benign	0.042
Sift	Benign	0.20	T
Sift4G	Uncertain	0.017	D
Vest4		0.13
MutPred		0.23		Gain of phosphorylation at P101 (P = 0.0124)
MVP		0.055
MPC		0.045
ClinPred		0.26	T
GERP RS		0.51
gMVP		0.0095
Mutation Taster		=98/2	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.080		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: rs782659658; hg19: chrX-49173740;