chrX-49304887-C-T

Variant names:

• chrX-49304887-C-T
• rs782348477
• NM_001098413.4:c.28C>T

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Moderate BS2

The NM_001098413.4(GAGE10):​c.28C>T​(p.Arg10Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000248 in 1,207,803 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 8 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 (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R10Q) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000062 (0 hom., 1 hem., cov: 26)
  • Exomes 𝑓: 0.000021 (0 hom. 7 hem.)
• Consequence: GAGE10 NM_001098413.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.0720
• Publications: 2 publications found

Genes affected

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

ACMG classification

Our verdict: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.07687846).
• BS2: High Hemizygotes in GnomAdExome4 at 7 gene

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.28C>T	p.Arg10Trp	missense	Exon 2 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.28C>T	p.Arg10Trp	missense	Exon 2 of 5	ENSP00000385415.3	A6NGK3

Frequencies

GnomAD3 genomes AF: 0.0000620 AC: 7 AN: 112820 Hom.: 0 Cov.: 26

Gnomad AFR AF: 0.000161

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000933

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000361

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000437 AC: 8 AN: 183162 AF XY: 0.0000296

Gnomad AFR exome AF: 0.000152

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: 0.0000366

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000210 AC: 23 AN: 1094983 Hom.: 0 Cov.: 41 AF XY: 0.0000194 AC XY: 7 AN XY: 361153

African (AFR) AF: 0.000152 AC: 4 AN: 26336

American (AMR) AF: 0.00 AC: 0 AN: 35196

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19362

East Asian (EAS) AF: 0.00 AC: 0 AN: 30188

South Asian (SAS) AF: 0.0000740 AC: 4 AN: 54072

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3554

European-Non Finnish (NFE) AF: 0.0000155 AC: 13 AN: 839917

Other (OTH) AF: 0.0000435 AC: 2 AN: 45938

GnomAD4 genome AF: 0.0000620 AC: 7 AN: 112820 Hom.: 0 Cov.: 26 AF XY: 0.0000286 AC XY: 1 AN XY: 34958

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

African (AFR) AF: 0.000161 AC: 5 AN: 31051

American (AMR) AF: 0.0000933 AC: 1 AN: 10720

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2656

East Asian (EAS) AF: 0.00 AC: 0 AN: 3623

South Asian (SAS) AF: 0.000361 AC: 1 AN: 2771

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6190

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 240

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 53362

Other (OTH) AF: 0.00 AC: 0 AN: 1519

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.000000481679), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00 Hom.: 0

ExAC AF: 0.0000412 AC: 5

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	0.12
BayesDel_addAF	Benign	-0.62	T
BayesDel_noAF	Benign	-0.87
CADD	Benign	11
DANN	Benign	0.67
FATHMM_MKL	Benign	0.0016	N
M_CAP	Benign	0.0012	T
MetaRNN	Benign	0.077	T
MetaSVM	Benign	-1.0	T
PhyloP100		-0.072
PrimateAI	Benign	0.41	T
PROVEAN	Pathogenic	-5.3	D
REVEL	Benign	0.031
Sift	Uncertain	0.021	D
Sift4G	Benign	0.065	T
Vest4		0.065
MVP		0.12
MPC		0.0077
ClinPred		0.023	T
GERP RS		-1.9
gMVP		0.043

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: rs782348477; hg19: chrX-49161366; COSMIC: COSV68163950; COSMIC: COSV68163950;