chrX-152701168-G-C

Variant names:

• chrX-152701168-G-C
• rs2124945229
• NM_005362.4:c.336G>C

Variant summary

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

The NM_005362.4(MAGEA3):​c.336G>C​(p.Lys112Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 21)
  • Exomes 𝑓: 9.1e-7 (0 hom. 0 hem.)
  • Failed GnomAD Quality Control
• Consequence: MAGEA3 NM_005362.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.175
• Publications: 0 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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.336G>C	p.Lys112Asn	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.336G>C	p.Lys112Asn	missense	Exon 3 of 3	ENSP00000359301.3	P43357
	MAGEA3	ENST00000598245.2	TSL:2	c.336G>C	p.Lys112Asn	missense	Exon 3 of 3	ENSP00000473093.1	P43357
	MAGEA3	ENST00000933889.1		c.336G>C	p.Lys112Asn	missense	Exon 3 of 3	ENSP00000603948.1

Frequencies

GnomAD3 genomes Cov.: 21

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 9.12e-7 AC: 1 AN: 1096177 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 361571

African (AFR) AF: 0.00 AC: 0 AN: 26383

American (AMR) AF: 0.00 AC: 0 AN: 35153

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19354

East Asian (EAS) AF: 0.00 AC: 0 AN: 30154

South Asian (SAS) AF: 0.0000185 AC: 1 AN: 54005

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40309

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4131

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 840650

Other (OTH) AF: 0.00 AC: 0 AN: 46038

GnomAD4 genome Cov.: 21

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	Pathogenic	0.63
BayesDel_addAF	Benign	-0.35	T
BayesDel_noAF	Benign	-0.74
CADD	Benign	12
DANN	Benign	0.94
DEOGEN2	Uncertain	0.56	D
FATHMM_MKL	Benign	0.018	N
LIST_S2	Benign	0.84	T
M_CAP	Benign	0.0011	T
MetaRNN	Uncertain	0.51	D
MetaSVM	Benign	-1.0	T
PhyloP100		-0.17
PrimateAI	Uncertain	0.65	T
PROVEAN	Pathogenic	-4.6	D
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.014	D
Vest4		0.13
MutPred		0.56		Loss of MoRF binding (P = 0.059)
MVP		0.65
ClinPred		0.99	D
GERP RS		-1.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.79
gMVP		0.67
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: rs2124945229; hg19: chrX-151869646;