NM_001098406.4:c.26A>C

Variant names:

• chrX-49323219-A-C
• NM_001098406.4:c.26A>C

Variant summary

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

The NM_001098406.4(GAGE12J):​c.26A>C​(p.Tyr9Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 12/17 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. Y9C) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 19)
  • Exomes 𝑓: 0.0000050 (0 hom. 2 hem.)
  • Failed GnomAD Quality Control
• Consequence: GAGE12J NM_001098406.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.07

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=0.10430741).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GAGE12J	NM_001098406.4	c.26A>C	p.Tyr9Ser	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.26A>C	p.Tyr9Ser	missense_variant	Exon 2 of 5	1	NM_001098406.4	ENSP00000409832.2

Frequencies

GnomAD3 genomes Cov.: 19

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000497 AC: 5 AN: 1006953 Hom.: 0 Cov.: 31 AF XY: 0.00000633 AC XY: 2 AN XY: 315885

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: 0.00000651

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 19

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Dec 01, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.26A>C (p.Y9S) alteration is located in exon 2 (coding exon 1) of the GAGE12J gene. This alteration results from a A to C substitution at nucleotide position 26, causing the tyrosine (Y) at amino acid position 9 to be replaced by a serine (S). 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	0.14
BayesDel_addAF	Benign	-0.39	T
BayesDel_noAF	Benign	-0.80
CADD	Benign	14
DANN	Benign	0.82
FATHMM_MKL	Benign	0.0013	N
M_CAP	Benign	0.0013	T
MetaRNN	Benign	0.10	T
MetaSVM	Benign	-1.1	T
PROVEAN	Benign	-0.69	N
REVEL	Benign	0.079
Sift	Uncertain	0.014	D
Sift4G	Uncertain	0.014	D
Vest4		0.18
MutPred		0.31		Loss of sheet (P = 0.0457);
MVP		0.040
MPC		0.50
ClinPred		0.13	T
GERP RS		-1.9
gMVP		0.025

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chrX-49179698;