X-55452853-A-C

Position:

• chrX-55452853-A-C

Variant summary

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

The NM_014061.5(MAGEH1):​c.479A>C​(p.Glu160Ala) 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: 22)
• Consequence: MAGEH1 NM_014061.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.137

Genes affected

MAGEH1 (HGNC:24092): (MAGE family member H1) This gene belongs to the non-CT (non cancer/testis) subgroup of the melanoma-associated antigen (MAGE) superfamily. The encoded protein is likely associated with apoptosis, cell cycle arrest, growth inhibition or cell differentiation. The protein may be involved in the atRA (all-trans retinoic acid) signaling through the STAT1-alpha (signal transducer and activator of transcription 1-alpha) pathway. [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
MAGEH1	NM_014061.5	c.479A>C	p.Glu160Ala	missense_variant	1/1	ENST00000342972.3	NP_054780.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MAGEH1	ENST00000342972.3	c.479A>C	p.Glu160Ala	missense_variant	1/1	6	NM_014061.5	ENSP00000343706.1

Frequencies

GnomAD3 genomes Cov.: 22

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 22

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

Sep 30, 2021

The c.479A>C (p.E160A) alteration is located in exon 1 (coding exon 1) of the MAGEH1 gene. This alteration results from a A to C substitution at nucleotide position 479, causing the glutamic acid (E) at amino acid position 160 to be replaced by an alanine (A). 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	Pathogenic	0.72
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.58
CADD	Benign	14
DANN	Uncertain	0.98
DEOGEN2	Benign	0.35	T
FATHMM_MKL	Benign	0.031	N
LIST_S2	Uncertain	0.94	D
M_CAP	Benign	0.014	T
MetaRNN	Uncertain	0.51	D
MetaSVM	Benign	-1.1	T
MutationAssessor	Pathogenic	2.9	M
MutationTaster	Benign	1.0	N
PrimateAI	Uncertain	0.76	T
PROVEAN	Pathogenic	-5.8	D
REVEL	Benign	0.087
Sift	Uncertain	0.0040	D
Sift4G	Pathogenic	0.0	D
Polyphen		0.97	D
Vest4		0.23
MutPred		0.71		Loss of disorder (P = 0.111);
MVP		0.31
MPC		1.6
ClinPred		0.94	D
GERP RS		0.54
Varity_R		0.31
gMVP		0.77

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs200891712; hg19: chrX-55479286;