X-152766912-T-A

Position:

• chrX-152766912-T-A

Variant summary

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

The ENST00000329342.10(MAGEA6):​c.739A>T​(p.Thr247Ser) 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)
• Consequence: MAGEA6 ENST00000329342.10 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.54

Genes affected

MAGEA6 (HGNC:6804): (MAGE family member A6) 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. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Aug 2013]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MAGEA6	NM_005363.5	c.739A>T	p.Thr247Ser	missense_variant	3/3	ENST00000329342.10	NP_005354.1
MAGEA6	NM_175868.4	c.739A>T	p.Thr247Ser	missense_variant	3/3		NP_787064.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MAGEA6	ENST00000329342.10	c.739A>T	p.Thr247Ser	missense_variant	3/3	1	NM_005363.5	ENSP00000329199	P1
MAGEA6	ENST00000616035.4	c.739A>T	p.Thr247Ser	missense_variant	3/3	5		ENSP00000480637	P1
MAGEA6	ENST00000457643.1			downstream_gene_variant		3		ENSP00000401806

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

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 21, 2024

The c.739A>T (p.T247S) alteration is located in exon 3 (coding exon 1) of the MAGEA6 gene. This alteration results from a A to T substitution at nucleotide position 739, causing the threonine (T) at amino acid position 247 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	0.22
BayesDel_addAF	Benign	-0.31	T
BayesDel_noAF	Benign	-0.68
CADD	Benign	15
DANN	Benign	0.97
DEOGEN2	Benign	0.11	T;T
FATHMM_MKL	Benign	0.049	N
LIST_S2	Benign	0.73	.;T
M_CAP	Benign	0.00081	T
MetaRNN	Uncertain	0.71	D;D
MetaSVM	Benign	-1.1	T
MutationTaster	Benign	1.0	N;N
PrimateAI	Benign	0.44	T
PROVEAN	Uncertain	-3.8	D;.
Sift	Uncertain	0.019	D;.
Sift4G	Uncertain	0.0060	D;D
Vest4		0.14
MutPred		0.88		Gain of disorder (P = 0.0544);Gain of disorder (P = 0.0544);
MVP		0.47
ClinPred		0.98	D
GERP RS		1.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.41
gMVP		0.47

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-151935428;