chrX-55452878-C-A

Variant names:

• chrX-55452878-C-A
• rs2031198539
• NM_014061.5:c.504C>A

Variant summary

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

The NM_014061.5(MAGEH1):​c.504C>A​(p.His168Gln) 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. 12/21 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: MAGEH1 NM_014061.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.335
• Publications: 0 publications found

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

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=0.25421792).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014061.5. 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
	MAGEH1	NM_014061.5	MANE Select	c.504C>A	p.His168Gln	missense	Exon 1 of 1	NP_054780.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAGEH1	ENST00000342972.3	TSL:6 MANE Select	c.504C>A	p.His168Gln	missense	Exon 1 of 1	ENSP00000343706.1	Q9H213

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 23

Alfa AF: 0.00 Hom.: 0

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	Uncertain	0.56
BayesDel_addAF	Benign	-0.42	T
BayesDel_noAF	Benign	-0.84
CADD	Benign	9.3
DANN	Benign	0.89
DEOGEN2	Benign	0.15	T
FATHMM_MKL	Benign	0.089	N
LIST_S2	Benign	0.58	T
M_CAP	Benign	0.0051	T
MetaRNN	Benign	0.25	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.8	L
PhyloP100		-0.34
PrimateAI	Pathogenic	0.83	D
PROVEAN	Uncertain	-3.7	D
REVEL	Benign	0.020
Sift	Uncertain	0.017	D
Sift4G	Benign	0.12	T
Polyphen		0.62	P
Vest4		0.20
MutPred		0.34		Gain of MoRF binding (P = 0.1039)
MVP		0.56
MPC		1.5
ClinPred		0.71	D
GERP RS		1.2
Varity_R		0.24
gMVP		0.32
Mutation Taster		=97/3	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: rs2031198539; hg19: chrX-55479311;