chrX-152701175-G-C

Variant names:

• chrX-152701175-G-C
• rs1248162986
• NM_005362.4:c.343G>C

Variant summary

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

The NM_005362.4(MAGEA3):​c.343G>C​(p.Glu115Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000913 in 1,095,600 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. In-silico tool predicts a benign outcome for this variant. 6/8 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. E115K) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 21)
  • Exomes 𝑓: 9.1e-7 (0 hom. 0 hem.)
• Consequence: MAGEA3 NM_005362.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.509
• Publications: 1 publications found

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

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=0.13802862).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005362.4. 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
	MAGEA3	NM_005362.4	MANE Select	c.343G>C	p.Glu115Gln	missense	Exon 3 of 3	NP_005353.1	P43357

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAGEA3	ENST00000370278.4	TSL:1 MANE Select	c.343G>C	p.Glu115Gln	missense	Exon 3 of 3	ENSP00000359301.3	P43357
	MAGEA3	ENST00000598245.2	TSL:2	c.343G>C	p.Glu115Gln	missense	Exon 3 of 3	ENSP00000473093.1	P43357
	MAGEA3	ENST00000933889.1		c.343G>C	p.Glu115Gln	missense	Exon 3 of 3	ENSP00000603948.1

Frequencies

GnomAD3 genomes Cov.: 21

GnomAD4 exome AF: 9.13e-7 AC: 1 AN: 1095600 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 361358

African (AFR) AF: 0.00 AC: 0 AN: 26379

American (AMR) AF: 0.00 AC: 0 AN: 35152

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19351

East Asian (EAS) AF: 0.00 AC: 0 AN: 30147

South Asian (SAS) AF: 0.00 AC: 0 AN: 53995

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40300

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4127

European-Non Finnish (NFE) AF: 0.00000119 AC: 1 AN: 840144

Other (OTH) AF: 0.00 AC: 0 AN: 46005

GnomAD4 genome Cov.: 21

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
CADD	Benign	15
DEOGEN2	Benign	0.18	T
LIST_S2	Benign	0.49	T
MetaRNN	Benign	0.14	T
PhyloP100		0.51
PROVEAN	Benign	-1.7	N
Sift	Benign	0.42	T
Sift4G	Benign	0.13	T
Vest4		0.12
gMVP		0.32
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

dbSNP: rs1248162986; COSMIC: COSV100939017;