Variant X-55452987-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_014061.5(MAGEH1):c.613G>A(p.Val205Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000546 in 1,097,962 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 1 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 22)

Exomes 𝑓: 0.0000055 ( 0 hom. 1 hem. )

Consequence

MAGEH1
NM_014061.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.69

Variant links:

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]

MAGEH1 links:

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ACMG classification

Classification made for transcript

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=0.112553835).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MAGEH1	NM_014061.5 linkuse as main transcript	c.613G>A	p.Val205Ile	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 linkuse as main transcript	c.613G>A	p.Val205Ile	missense_variant	1/1		NM_014061.5	ENSP00000343706	P1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000273

AC:

AN:

183008

Hom.:

AF XY:

0.0000148

AC XY:

AN XY:

67536

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000361

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000546

AC:

AN:

1097962

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

363322

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000166

Gnomad4 SAS exome

AF:

0.0000185

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.0000165

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 03, 2023

The c.613G>A (p.V205I) alteration is located in exon 1 (coding exon 1) of the MAGEH1 gene. This alteration results from a G to A substitution at nucleotide position 613, causing the valine (V) at amino acid position 205 to be replaced by an isoleucine (I). 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

0.13

BayesDel_addAF

Benign

-0.65

BayesDel_noAF

Benign

-0.85

CADD

Uncertain

DANN

Benign

0.97

DEOGEN2

Benign

0.083

FATHMM_MKL

Benign

0.36

LIST_S2

Benign

0.66

M_CAP

Benign

0.0065

MetaRNN

Benign

0.11

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.0

MutationTaster

Benign

1.0

PrimateAI

Pathogenic

0.81

PROVEAN

Benign

-0.67

REVEL

Benign

0.066

Sift

Benign

0.043

Sift4G

Benign

0.15

Polyphen

0.48

Vest4

0.18

MutPred

0.33

Loss of helix (P = 0.1299);

MVP

0.65

MPC

0.56

ClinPred

0.12

GERP RS

2.6

Varity_R

0.090

gMVP

0.22

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over