Variant X-27821648-A-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_182506.3(MAGEB10):c.342A>C(p.Lys114Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000128 in 1,098,020 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 7 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 23)

Exomes 𝑓: 0.000013 ( 0 hom. 7 hem. )

Consequence

MAGEB10
NM_182506.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.00100

Variant links:

Genes affected

MAGEB10 (HGNC:25377): (MAGE family member B10) This gene encodes a member of the B subfamily of the melanoma associated antigen protein family. The encoded protein is specifically expressed in testis and tumor cells. [provided by RefSeq, Apr 2010]

MAGEB10 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.15500182).

BS2

High Hemizygotes in GnomAdExome4 at 7 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MAGEB10	NM_182506.3 linkuse as main transcript	c.342A>C	p.Lys114Asn	missense_variant	3/3	ENST00000356790.2	NP_872312.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MAGEB10	ENST00000356790.2 linkuse as main transcript	c.342A>C	p.Lys114Asn	missense_variant	3/3	1	NM_182506.3	ENSP00000368304	P1
MAGEB10	ENST00000614159.1 linkuse as main transcript	c.342A>C	p.Lys114Asn	missense_variant	1/1			ENSP00000480889	P1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000274

AC:

AN:

182503

Hom.:

AF XY:

0.0000448

AC XY:

AN XY:

67031

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000264

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000128

AC:

AN:

1098020

Hom.:

Cov.:

AF XY:

0.0000193

AC XY:

AN XY:

363382

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000185

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000119

Gnomad4 OTH exome

AF:

0.0000651

GnomAD4 genome

Cov.:

ExAC

AF:

0.0000659

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

Jun 05, 2023

The c.342A>C (p.K114N) alteration is located in exon 3 (coding exon 1) of the MAGEB10 gene. This alteration results from a A to C substitution at nucleotide position 342, causing the lysine (K) at amino acid position 114 to be replaced by an asparagine (N). 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

Uncertain

0.43

BayesDel_addAF

Benign

-0.54

BayesDel_noAF

Benign

-0.72

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.22

T;T

FATHMM_MKL

Benign

0.0038

LIST_S2

Benign

0.46

.;T

M_CAP

Benign

0.0016

MetaRNN

Benign

0.16

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.9

M;M

MutationTaster

Benign

1.0

PrimateAI

Benign

0.39

PROVEAN

Uncertain

-4.0

D;.

REVEL

Benign

0.13

Sift

Uncertain

0.0040

D;.

Sift4G

Uncertain

0.0030

D;D

Polyphen

0.99

D;D

Vest4

0.19

MutPred

0.56

Loss of methylation at K114 (P = 0.0177);Loss of methylation at K114 (P = 0.0177);

MVP

0.21

MPC

1.2

ClinPred

0.71

GERP RS

-4.2

Varity_R

0.45

gMVP

0.81

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

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