chrX-49317261-C-A

Position:

• chrX-49317261-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 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. 12/18 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

Genes affected

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

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.09311211).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GAGE10	NM_001098413.4	c.301C>A	p.Pro101Thr	missense_variant	4/5	ENST00000407599.4	NP_001091883.3
GAGE10	XM_024452325.1	c.259C>A	p.Pro87Thr	missense_variant	2/3		XP_024308093.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GAGE10	ENST00000407599.4	c.301C>A	p.Pro101Thr	missense_variant	4/5	5	NM_001098413.4	ENSP00000385415.3

Frequencies

GnomAD3 genomes Cov.: 22

GnomAD3 exomes AF: 0.00000545 AC: 1 AN: 183379 Hom.: 0 AF XY: 0.0000147 AC XY: 1 AN XY: 67841

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 SAS 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

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000119

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 22

Bravo AF: 0.00000756

ExAC AF: 0.0000165 AC: 2

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 12, 2024

The c.301C>A (p.P101T) alteration is located in exon 4 (coding exon 3) of the GAGE10 gene. This alteration results from a C to A substitution at nucleotide position 301, causing the proline (P) at amino acid position 101 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

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
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

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

Publications

LitVar

Other links and lift over

dbSNP: rs782659658; hg19: chrX-49173740;