X-49305467-C-T

Variant names:

• chrX-49305467-C-T
• rs5906771
• NM_001098413.4:c.145C>T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_001098413.4(GAGE10):​c.145C>T​(p.Arg49Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000181 in 110,200 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. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.000018 (0 hom., 0 hem., cov: 29)
  • Exomes 𝑓: 0.000020 (0 hom. 2 hem.)
  • Failed GnomAD Quality Control
• Consequence: GAGE10 NM_001098413.4 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.497
• Publications: 1 publications found

Genes affected

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

ACMG classification

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

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.060540706).
• BP6: Variant X-49305467-C-T is Benign according to our data. Variant chrX-49305467-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 3280454.Status of the report is criteria_provided_single_submitter, 1 stars.

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.145C>T	p.Arg49Cys	missense	Exon 3 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.145C>T	p.Arg49Cys	missense	Exon 3 of 5	ENSP00000385415.3	A6NGK3

Frequencies

GnomAD3 genomes AF: 0.0000181 AC: 2 AN: 110200 Hom.: 0 Cov.: 29

Gnomad AFR AF: 0.0000686

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: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000206 AC: 2 AN: 97056 AF XY: 0.0000425

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000222

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000195 AC: 21 AN: 1074559 Hom.: 0 Cov.: 32 AF XY: 0.00000570 AC XY: 2 AN XY: 351125

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

African (AFR) AF: 0.0000394 AC: 1 AN: 25391

American (AMR) AF: 0.0000592 AC: 2 AN: 33758

Ashkenazi Jewish (ASJ) AF: 0.000105 AC: 2 AN: 19099

East Asian (EAS) AF: 0.000100 AC: 3 AN: 29878

South Asian (SAS) AF: 0.0000188 AC: 1 AN: 53109

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 29254

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2846

European-Non Finnish (NFE) AF: 0.0000108 AC: 9 AN: 835761

Other (OTH) AF: 0.0000660 AC: 3 AN: 45463

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.0000000000000134337), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.0000181 AC: 2 AN: 110200 Hom.: 0 Cov.: 29 AF XY: 0.00 AC XY: 0 AN XY: 32612

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

African (AFR) AF: 0.0000686 AC: 2 AN: 29170

American (AMR) AF: 0.00 AC: 0 AN: 10481

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2638

East Asian (EAS) AF: 0.00 AC: 0 AN: 3561

South Asian (SAS) AF: 0.00 AC: 0 AN: 2746

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6096

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 239

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 53098

Other (OTH) AF: 0.00 AC: 0 AN: 1487

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.00000000770867), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00 Hom.: 1

ClinVar

ClinVar submissions

Significance: Likely benign

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	0.073
BayesDel_addAF	Benign	-0.49	T
BayesDel_noAF	Benign	-0.94
CADD	Benign	6.9
DANN	Benign	0.84
FATHMM_MKL	Benign	0.0011	N
M_CAP	Benign	0.0055	T
MetaRNN	Benign	0.061	T
MetaSVM	Benign	-0.99	T
PhyloP100		-0.50
PrimateAI	Benign	0.38	T
PROVEAN	Benign	-0.58	N
REVEL	Benign	0.012
Sift	Benign	0.060	T
Sift4G	Uncertain	0.043	D
Vest4		0.066
MutPred		0.26		Loss of solvent accessibility (P = 0.0703)
MVP		0.088
MPC		0.0074
ClinPred		0.035	T
GERP RS		-2.4
gMVP		0.014

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: rs5906771; hg19: chrX-49161946; COSMIC: COSV68164417; COSMIC: COSV68164417;