X-49323227-C-G

Variant names:

• chrX-49323227-C-G
• NM_001098406.4:c.34C>G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001098406.4(GAGE12J):​c.34C>G​(p.Pro12Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 11/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 20)
  • Exomes 𝑓: 0.0 (0 hom. 0 hem.)
  • Failed GnomAD Quality Control
• Consequence: GAGE12J NM_001098406.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.654

Genes affected

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

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.23585668).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GAGE12J	NM_001098406.4	c.34C>G	p.Pro12Ala	missense_variant	Exon 2 of 5	ENST00000442437.3	NP_001091876.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GAGE12J	ENST00000442437.3	c.34C>G	p.Pro12Ala	missense_variant	Exon 2 of 5	1	NM_001098406.4	ENSP00000409832.2

Frequencies

GnomAD3 genomes Cov.: 20

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 1033417 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 321541

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: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 20

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Nov 15, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.34C>G (p.P12A) alteration is located in exon 2 (coding exon 1) of the GAGE12J gene. This alteration results from a C to G substitution at nucleotide position 34, causing the proline (P) at amino acid position 12 to be replaced by an alanine (A). 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	0.16
BayesDel_addAF	Benign	-0.42	T
BayesDel_noAF	Benign	-0.84
CADD	Benign	1.8
DANN	Benign	0.69
FATHMM_MKL	Benign	0.0030	N
M_CAP	Benign	0.0018	T
MetaRNN	Benign	0.24	T
MetaSVM	Benign	-1.0	T
PROVEAN	Uncertain	-4.1	D
REVEL	Benign	0.022
Sift	Uncertain	0.023	D
Sift4G	Benign	0.17	T
Vest4		0.15
MutPred		0.52		Loss of glycosylation at P12 (P = 0.0399);
MVP		0.072
MPC		0.080
ClinPred		0.18	T
GERP RS		0.68
gMVP		0.014

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chrX-49179706;