X-152701181-G-A

Variant names:

• chrX-152701181-G-A
• NM_005362.4:c.349G>A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_005362.4(MAGEA3):​c.349G>A​(p.Val117Ile) 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 21)
• Consequence: MAGEA3 NM_005362.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.0780

Genes affected

MAGEA3 (HGNC:6801): (MAGE family member A3) This gene is a member of the MAGEA gene family. The members of this family encode proteins with 50 to 80% sequence identity to each other. The promoters and first exons of the MAGEA genes show considerable variability, suggesting that the existence of this gene family enables the same function to be expressed under different transcriptional controls. The MAGEA genes are clustered at chromosomal location Xq28. They have been implicated in some hereditary disorders, such as dyskeratosis congenita. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.24780014).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAGEA3	NM_005362.4	c.349G>A	p.Val117Ile	missense_variant	Exon 3 of 3	ENST00000370278.4	NP_005353.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MAGEA3	ENST00000370278.4	c.349G>A	p.Val117Ile	missense_variant	Exon 3 of 3	1	NM_005362.4	ENSP00000359301.3
MAGEA3	ENST00000598245.2	c.349G>A	p.Val117Ile	missense_variant	Exon 3 of 3	2		ENSP00000473093.1
MAGEA3	ENST00000417212.5	c.349G>A	p.Val117Ile	missense_variant	Exon 3 of 3	2		ENSP00000392758.1

Frequencies

GnomAD3 genomes Cov.: 21

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 21

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jan 30, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.349G>A (p.V117I) alteration is located in exon 3 (coding exon 1) of the MAGEA3 gene. This alteration results from a G to A substitution at nucleotide position 349, causing the valine (V) at amino acid position 117 to be replaced by an isoleucine (I). 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	-0.40	T
BayesDel_noAF	Benign	-0.81
CADD	Benign	8.6
DANN	Uncertain	0.99
DEOGEN2	Benign	0.19	T;T;T
FATHMM_MKL	Benign	0.021	N
LIST_S2	Benign	0.63	.;T;T
M_CAP	Benign	0.0012	T
MetaRNN	Benign	0.25	T;T;T
MetaSVM	Benign	-1.1	T
PrimateAI	Uncertain	0.65	T
PROVEAN	Benign	-0.73	N;N;.
Sift	Uncertain	0.021	D;D;.
Sift4G	Uncertain	0.052	T;T;T
Vest4		0.16
MutPred		0.68		Gain of catalytic residue at L122 (P = 0.0792);Gain of catalytic residue at L122 (P = 0.0792);Gain of catalytic residue at L122 (P = 0.0792);
MVP		0.41
ClinPred		0.37	T
GERP RS		-0.58
Varity_R		0.23
gMVP		0.38

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-151869659;