X-152135601-C-T

Position:

• chrX-152135601-C-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The ENST00000370323.9(MAGEA10):​c.20G>A​(p.Arg7His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000784 in 1,135,595 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 28 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R7C) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.00012 (0 hom., 5 hem., cov: 23)
  • Exomes 𝑓: 0.000074 (0 hom. 23 hem.)
• Consequence: MAGEA10 ENST00000370323.9 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.489

Genes affected

MAGEA10 (HGNC:6797): (MAGE family member A10) 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. Read-through transcription also exists between this gene and the downstream melanoma antigen family A, 5 (MAGEA5) gene.[provided by RefSeq, Oct 2011]

LOC100533997 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.03603977).
• BP6: Variant X-152135601-C-T is Benign according to our data. Variant chrX-152135601-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2661666.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Hemizygotes in GnomAd4 at 5 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MAGEA10	NM_021048.5	c.20G>A	p.Arg7His	missense_variant	4/4	ENST00000370323.9	NP_066386.3
LOC100533997	NM_001204811.3	c.-278+2874G>A		intron_variant			NP_001191740.1
MAGEA10	NM_001011543.3	c.20G>A	p.Arg7His	missense_variant	5/5		NP_001011543.3
MAGEA10	NM_001251828.2	c.20G>A	p.Arg7His	missense_variant	5/5		NP_001238757.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MAGEA10	ENST00000370323.9	c.20G>A	p.Arg7His	missense_variant	4/4	1	NM_021048.5	ENSP00000359347	P1

Frequencies

GnomAD3 genomes AF: 0.000116 AC: 13 AN: 112312 Hom.: 0 Cov.: 23 AF XY: 0.000145 AC XY: 5 AN XY: 34460

Gnomad AFR AF: 0.0000324

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000936

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000370

Gnomad FIN AF: 0.000969

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000752

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.0000846 AC: 11 AN: 130004 Hom.: 0 AF XY: 0.000112 AC XY: 5 AN XY: 44840

Gnomad AFR exome AF: 0.0000829

Gnomad AMR exome AF: 0.0000610

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.000319

Gnomad NFE exome AF: 0.0000805

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000743 AC: 76 AN: 1023232 Hom.: 0 Cov.: 31 AF XY: 0.0000707 AC XY: 23 AN XY: 325164

Gnomad4 AFR exome AF: 0.000338

Gnomad4 AMR exome AF: 0.0000433

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000338

Gnomad4 SAS exome AF: 0.0000241

Gnomad4 FIN exome AF: 0.000346

Gnomad4 NFE exome AF: 0.0000608

Gnomad4 OTH exome AF: 0.0000468

GnomAD4 genome AF: 0.000116 AC: 13 AN: 112363 Hom.: 0 Cov.: 23 AF XY: 0.000145 AC XY: 5 AN XY: 34521

Gnomad4 AFR AF: 0.0000323

Gnomad4 AMR AF: 0.0000935

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000371

Gnomad4 FIN AF: 0.000969

Gnomad4 NFE AF: 0.0000752

Gnomad4 OTH AF: 0.00

Alfa AF: 0.0000453 Hom.: 0

Bravo AF: 0.0000340

TwinsUK AF: 0.00 AC: 0

ALSPAC AF: 0.000346 AC: 1

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000149 AC: 1

ExAC AF: 0.0000952 AC: 11

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Mar 01, 2023

MAGEA10: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_addAF	Benign	-0.51	T
BayesDel_noAF	Benign	-0.78
CADD	Benign	8.1
DANN	Benign	0.88
DEOGEN2	Benign	0.0077	T;T;T;T;.;.
FATHMM_MKL	Benign	0.045	N
LIST_S2	Benign	0.62	.;T;T;T;T;T
M_CAP	Benign	0.0057	T
MetaRNN	Benign	0.036	T;T;T;T;T;T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	1.6	L;L;.;.;.;.
MutationTaster	Benign	1.0	N;N
PrimateAI	Benign	0.48	T
PROVEAN	Benign	-0.62	N;N;N;N;.;.
REVEL	Benign	0.067
Sift	Benign	0.23	T;T;D;T;.;.
Sift4G	Benign	0.18	T;T;.;.;D;.
Polyphen		0.42	B;B;.;.;.;.
Vest4		0.20
MVP		0.38
MPC		0.48
ClinPred		0.043	T
GERP RS		0.55
Varity_R		0.034
gMVP		0.12

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

Other links and lift over

dbSNP: rs145553450; hg19: chrX-151304073; COSMIC: COSV54884254; COSMIC: COSV54884254;