chrX-49323270-C-T

Variant names:

• chrX-49323270-C-T
• NM_001098406.4:c.77C>T

Variant summary

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

The NM_001098406.4(GAGE12J):​c.77C>T​(p.Pro26Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 11/18 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. P26S) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 20)
• Consequence: GAGE12J NM_001098406.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.616
• Publications: 0 publications found

Genes affected

GAGE12J (HGNC:17778): (G antigen 12J)

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=0.22165653).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001098406.4. 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
	GAGE12J	NM_001098406.4	MANE Select	c.77C>T	p.Pro26Leu	missense	Exon 2 of 5	NP_001091876.2	A6NER3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GAGE12J	ENST00000442437.3	TSL:1 MANE Select	c.77C>T	p.Pro26Leu	missense	Exon 2 of 5	ENSP00000409832.2	A6NER3

Frequencies

GnomAD3 genomes Cov.: 20

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 20

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	0.18
BayesDel_addAF	Benign	-0.44	T
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.97
DANN	Uncertain	0.99
FATHMM_MKL	Benign	0.0036	N
M_CAP	Benign	0.0019	T
MetaRNN	Benign	0.22	T
MetaSVM	Benign	-1.1	T
PhyloP100		-0.62
PROVEAN	Pathogenic	-5.2	D
REVEL	Benign	0.026
Sift	Benign	0.19	T
Sift4G	Benign	0.11	T
Vest4		0.17
MutPred		0.57		Gain of helix (P = 0.1736)
MVP		0.095
MPC		0.43
ClinPred		0.98	D
GERP RS		-1.4
gMVP		0.020
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

hg19: chrX-49179749;