X-149716401-T-A

Position:

• chrX-149716401-T-A

Variant summary

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

The ENST00000355220.6(MAGEA11):​c.915T>A​(p.Asn305Lys) 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. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 23)
• Consequence: MAGEA11 ENST00000355220.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.639

Genes affected

MAGEA11 (HGNC:6798): (MAGE family member A11) 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. Two transcript variants encoding different isoforms have been found for this gene. [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=0.1336436).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MAGEA11	NM_005366.5	c.915T>A	p.Asn305Lys	missense_variant	5/5	ENST00000355220.6	NP_005357.2
MAGEA11	NM_001011544.2	c.828T>A	p.Asn276Lys	missense_variant	5/5		NP_001011544.1
MAGEA11	XM_047442106.1	c.915T>A	p.Asn305Lys	missense_variant	8/8		XP_047298062.1
MAGEA11	XM_011531164.3	c.891T>A	p.Asn297Lys	missense_variant	4/4		XP_011529466.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MAGEA11	ENST00000355220.6	c.915T>A	p.Asn305Lys	missense_variant	5/5	1	NM_005366.5	ENSP00000347358	P2
MAGEA11	ENST00000333104.8	c.828T>A	p.Asn276Lys	missense_variant	4/4	5		ENSP00000328177	A2
MAGEA11	ENST00000412632.6	c.828T>A	p.Asn276Lys	missense_variant	5/5	2		ENSP00000391496
MAGEA11	ENST00000518694.1	n.2505T>A		non_coding_transcript_exon_variant	7/7	2

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 23

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 13, 2023

The c.915T>A (p.N305K) alteration is located in exon 5 (coding exon 4) of the MAGEA11 gene. This alteration results from a T to A substitution at nucleotide position 915, causing the asparagine (N) at amino acid position 305 to be replaced by a lysine (K). 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	0.22
BayesDel_addAF	Benign	-0.48	T
BayesDel_noAF	Benign	-0.93
CADD	Benign	13
DANN	Benign	0.86
DEOGEN2	Benign	0.017	.;T;T
FATHMM_MKL	Benign	0.035	N
LIST_S2	Benign	0.24	T;T;T
M_CAP	Benign	0.0013	T
MetaRNN	Benign	0.13	T;T;T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	0.88	.;.;L
MutationTaster	Benign	1.0	N;N
PrimateAI	Benign	0.33	T
PROVEAN	Benign	-2.3	N;D;D
REVEL	Benign	0.050
Sift	Uncertain	0.024	D;D;T
Sift4G	Uncertain	0.038	D;D;D
Polyphen		0.015, 0.064	.;B;B
Vest4		0.076, 0.084
MutPred		0.51		.;.;Gain of methylation at N305 (P = 0.0013);
MVP		0.21
MPC		0.29
ClinPred		0.069	T
GERP RS		0.91
Varity_R		0.16
gMVP		0.51

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-148798061;